Pills

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Pills are pickups that can provide useful or inhibiting effects. They take up the same slot as cards and runes.

At the start of each run, an effect is randomly assigned to each color of pill. The pill effect for each color will remain constant throughout the run. (However, it is possible for Collectible PHD icon.pngPHD, Collectible Virgo icon.pngVirgo, (in Repentance and Repentance+)Collectible False PHD icon.pngFalse PHD, or (in Repentance and Repentance+)Collectible Lucky Foot icon.pngLucky Foot to reassign some of the effects, such that 2 different colored pills will have the same effect.) Pills start the game unidentified (unless the player is holding Collectible PHD icon.pngPHD or (in Repentance and Repentance+)Collectible False PHD icon.pngFalse PHD); their effect is shown as "???" when picked up. Upon using a particular pill for the first time, its effect will be revealed and all subsequent pills with the same color will have their effect shown as well. The set of pill effects for any given run is usually known as the pill pool.

  • (except in Rebirth) The pill pool for each run has increased from 9 to 13.

Pill Effects

ID Pill (in Repentance and Repentance+) Polarity (in Repentance and Repentance+) Class Effect (in Repentance and Repentance+) Horse Pill Effect
0 Bad Gas N 1 Isaac farts, dealing 5 damage and poisoning enemies around him. The poison affects all enemies in the room.
1 Bad Trip - 2 Deals a full heart of damage to Isaac. Using a Bad Trip pill while Isaac only has a single heart left or less turns it into a Full Health pill.
(in Repentance and Repentance+) This doesn't count as damage for the purposes of Devil RoomDevil Room/Angel RoomAngel Room generation odds or score reduction.
Deals two hearts of damage. If Isaac would not survive, the pill becomes Full Health.
2 Balls of Steel + 2 Grants Isaac two soul hearts. Grants four soul hearts.
3 Bombs Are Key N 2 Swaps the values of Isaac's Bomb.pngBombs and Key.pngKeys.
(in Repentance and Repentance+)The effects of (except in Rebirth) Golden Bomb.pngGolden Bombs and Golden Key.pngGolden Keys are also swapped.
The number of bombs and keys is increased by 50% while swapping.
4 Explosive Diarrhea N 1 Spawns a lit bomb behind Isaac every second for five seconds. Spawns more bombs with the effects of Collectible Mr. Mega icon.pngMr. Mega and Collectible Bobby-Bomb icon.pngBobby-Bomb.
5 Full Health + 2 Refills every empty red heart container. Fully heals and grants 3 soul hearts.
6 Health Down - 3 Removes one red heart container. Acts as a Health Up pill if Isaac has one or fewer red heart containers. Characters who cannot have red heart containers will lose one heart. Removes two heart containers. if Isaac has 0 or 1 heart containers, the pill becomes Health Up and if he has 2 with no other types of health, they are removed and he is given half a soul heart.
7 Health Up + 3 Adds one empty red heart container. Adds two empty red heart containers.
8 I Found Pills N 0 Changes the appearance of Isaac's face. This pill is cosmetic only, (in Rebirth)and the effect disappears when Isaac leaves the room. Isaac's face gets a permanent, very exaggerated expression resembling a horse.
9 Puberty N 0 Causes Isaac to grow four hairs from the top of his head and zits on his face. This pill is cosmetic only and will stay for the rest of the run.
(except in Rebirth and Afterbirth) Consuming three puberty pills will grant the AdultAdult transformation, granting one red heart container and making Isaac's voice slightly deeper (one time effect).
Isaac gains very fluffy hair covering his entire head and even face.
10 Pretty Fly + 2 Grants a fly orbital, up to 3 maximum, that circles the player, blocking projectiles and damaging fly-type enemies on touch. Spawns a Collectible Big Fan icon.pngBig Fan. There is no upper limit. These Big Fans do not contribute towards the BeelzebubBeelzebub transformation.
11 Range Down - 3 (except in Repentance and Repentance+)-2.00 range.
(in Repentance and Repentance+)-1.00 range.
-2.00 range.
12 Range Up + 3 (except in Repentance and Repentance+)+2.50 range.
(in Repentance and Repentance+)+1.25 range.
+2.50 range.
13 Speed Down - 3 -0.12 speed. -0.24 speed.
14 Speed Up + 3 +0.15 speed. +0.30 speed.
15 Tears Down - 3 -0.28 tears. -0.56 tears.
16 Tears Up + 3 +0.35 tears. +0.70 tears.
17 Luck Down - 3 -1 luck. -2 luck.
18 Luck Up + 3 +1 luck. +2 luck.
19 Telepills N 1 Teleports Isaac to a random room. Has a small chance to teleport Isaac to the I AM ERRORI AM ERROR room, and an extremely small chance to teleport him to the Black MarketBlack Market, like Collectible Undefined icon.pngUndefined. (except in Repentance and Repentance+)Unobtainable in Greed Mode.

(in Repentance and Repentance+) Using a Telepills in the mirrored version of (in Repentance and Repentance+)DownpourDownpour/(in Repentance and Repentance+)DrossDross II has a chance to teleport Isaac to an Ultra Secret RoomUltra Secret Room.

No difference.
20 48 Hour Energy + 2 Drops one to two Lil' Battery.pngLil' Batteries and fully charges the spacebar item. (in Afterbirth and Afterbirth †) Can be used with Collectible Placebo icon.pngPlacebo or (except in Rebirth and Afterbirth)Collectible D1 icon.pngD1 to generate infinite batteries. Spawns 3-4 batteries.
21 Hematemesis N 2 Sets Isaac's red heart health to 1, then spawns 1-4 Red Heart.pngRed Hearts. This fills Isaac's first red heart container (even if Isaac's red health is less than 1) and empties the rest, including (except in Rebirth and Afterbirth) Bone Heart.pngBone Hearts. This effect does not count as damage. If used without any red heart containers, no health will be deducted, but red hearts will still spawn. If used in aSuper Secret RoomSuper Secret Room containing a Black Heart.pngBlack Heart or Eternal Heart.pngEternal Heart, it will spawn those types of hearts instead. Spawns 4-7 hearts.
22 Paralysis - 1 Prevents Isaac from moving and shooting for 2 seconds. The effect lasts 4 seconds.
23 I can see forever! + 2 Opens all entrances to the Secret RoomSecret Room and Super Secret RoomSuper Secret Room for the current floor. In addition to the normal effect, fully reveals the map like Collectible The Mind icon.pngThe Mind.
24 Pheromones + 1 Charms all enemies in the room for a short period of time. The charm is permanent, turning the enemies friendly.
25 Amnesia - 2 Replaces the floor map with a ? for the rest of the floor, identical to the effect of Curse of the Lost. If no other curses are active for the floor, the Curse of the Lost will appear under the level name when the map key is held. This effect can be negated by picking up Collectible Black Candle icon.pngBlack Candle, but will not prevent future uses of the Amnesia pill from giving the Curse of the Lost effect. (except in Rebirth) Also the only pill to have its flavor text appear on a piece of paper as curses do. No difference.
26 Lemon Party + 1 Spawns a large yellow pool (similar to Collectible Lemon Mishap icon.pngLemon Mishap) around Isaac. Greatly damages any enemy that steps on it, for 22 damage per tick or 66 damage per second. The puddle is larger, covering nearly the entire room if used near the center.
27 R U a Wizard? - 1 Tears are shot diagonally outwards for 30 seconds, making it much harder to aim. This effect will persist between rooms until it wears off. The effect lasts for 60 seconds.
(except in Rebirth) Afterbirth
28 Needs to be unlocked Percs! + 1 For the duration of the room, taking damage only removes a half-heart from Isaac's HP, regardless of the source of the damage. (Similar effect toCollectible The Wafer icon.pngThe Wafer's)
Unlocked by: (except in Rebirth)2 new pills Complete PAY TO PLAY (challenge #24).
No difference.
29 Needs to be unlocked Addicted! - 1 For the duration of the room, taking damage removes a full heart from Isaac's HP, regardless of the source of the damage. Also changes Isaac's appearance for the room.
Unlocked by: (except in Rebirth)2 new pills Complete PAY TO PLAY (challenge #24).
No difference.
30 Needs to be unlocked Re-Lax N 0 Spawns Poop.pngPoop at Isaac's position for a few seconds. A higher speed stat means Isaac can cover more tiles in poop in the same time. A pun on laxatives.
Unlocked by: (except in Rebirth)2 new pills Complete Have a Heart (challenge #25).
The effect lasts much longer.
31 Needs to be unlocked ??? - 1 Gives the Curse of the Maze effect for the remainder of the floor. The effect can stack with other curses. If no other curses are active for the floor, Curse of the Maze will appear under the level name when Tab is held. This effect can be negated by picking up Collectible Black Candle icon.pngBlack Candle, but will not prevent future uses of the ??? pill from giving the Curse of the Maze effect. As the pill's name is "???", the same as what unidentified pills are referred to, it is easy to accidentally use it more than once per run. It is recommended to memorize its color upon first using it.
Unlocked by: (except in Rebirth)2 new pills Complete Have a Heart (challenge #25).
No difference.
32 One makes you larger N 1 Increases Isaac's size and decreases the pitch of his voice. This effect does not increase the size of Isaac's hitbox, but increases the size of Character The Forgotten icon.pngThe Forgotten's bone club. (except in Rebirth and Afterbirth) These pills contribute to the Stompy transformation. Size increases by two steps.
33 One makes you small N 1 Decreases Isaac's size and increases the pitch of his voice. This effect decreases the size of Isaac's hitbox; a small enough hitbox allows Isaac to walk "under" certain projectiles to avoid them. Size decreases by two steps.
34 Infested! + 1 Destroys all poop in the room and spawns a single blue spider under Isaac and on each destroyed poop. Double the number of spiders spawned.
35 Infested? + 1 Spawns blue spiders equal to the number of enemies in the room. If there are no enemies in the room, spawns 1-3 Blue Spiders. Double the number of spiders spawned.
36 Power Pill! + 1 Temporarily grants invulnerability, inflicts fear on enemies in the room, lets Isaac deal contact damage, and has a chance to replenish a Half Red Heart.pngHalf Red Heart every time an enemy is killed, similar to Collectible The Gamekid icon.pngThe Gamekid. In addition to the normal effect, grants (except in Rebirth and Afterbirth)Huge GrowthHuge Growth for +7 flat damage and +3 range. The Huge Growth bonus persists after the Gamekid wears off.
37 Retro Vision - 1 (except in Repentance and Repentance+)Applies a pixelating filter on the screen 3 times over 30 seconds. The effect continues between floors.

(in Repentance and Repentance+)Pixelates the screen and degrades colors for 30 seconds.

The effect lasts 90 seconds, with no breaks.
38 Friends Till The End! + 1 Spawns three blue flies. Spawns 12 blue flies.
(except in Rebirth and Afterbirth) Afterbirth †
39 X-Lax - 0 Creates a pool of slippery brown creep underneath Isaac. The pool lasts much longer.
40 Something's wrong... + 0 Creates a pool of black creep beneath Isaac that slows enemies. The pool lasts much longer.
41 I'm Drowsy... N 1 (except in Repentance and Repentance+) Slows all enemies for the duration of the room.
(in Repentance and Repentance+) Applies the Collectible Stop Watch icon.pngStop Watch effect, slowing all enemies, Isaac, and the background music as well as additionally applying the Slowness status effect on every enemy for the duration of the room.
No difference.
42 I'm Excited!!! N 1 (except in Repentance and Repentance+) Increases the speed of all enemies for the duration of the room.
(in Repentance and Repentance+) Increases the speed of all enemies, Isaac, and the background music for the duration of the room.
The effect triggers again three additional times.
No difference.
43 Needs to be unlocked Gulp! + 2 Destroys any trinkets held by Isaac and grants their effects permanently.
Unlocked by: (except in Rebirth and Afterbirth)Once More with Feeling! Complete a Victory Lap by defeating The Lamb.
Heals one red heart per gulped trinket (Up to 2 at the same time with Collectible Mom's Purse icon.pngMom's Purse). No effect for characters who cannot have red hearts. This counts for two gulp pills toward the (except in Rebirth and Afterbirth)Collectible Marbles icon.pngMarbles achievement.
44 Needs to be unlocked Horf! N 0 Isaac shoots an explosive tear with the Collectible Ipecac icon.pngIpecac effect that always deals 200 damage.
Unlocked by: (except in Rebirth and Afterbirth)Dedication Participate in 31 Daily Challenges (they don't have to be consecutive; it will still count if Isaac dies in the first room).
Isaac shoots a cluster of 6 Horf! tears with 150-400 damage per tear, resulting in an average of 1650 damage if all tears or their explosions hit.
45 Needs to be unlocked Feels like I'm walking on sunshine! + 1 Temporarily makes Isaac invincible, similar to Collectible Unicorn Stump icon.pngUnicorn Stump.
Unlocked by: (except in Rebirth and Afterbirth)Sin collector Collect every entry in the Bestiary (bugged v190 - Mobs that don't exist in the bestiary are being counted. This allows Sin Collector to be unlocked without a complete bestiary).
The effect is upgraded to Collectible The Gamekid icon.pngThe Gamekid's.
46 Needs to be unlocked Vurp! + 2 Spawns the last pill used. Will spawn itself if no other pills were taken beforehand, or if Vurp! was the last pill used.
Unlocked by: (except in Rebirth and Afterbirth)U Broke It! Obtain 50 items in a run (duplicate passive items/familiars count towards the total, e.g., multiple Collectible Breakfast icon.pngBreakfast).
If the last pill was a normal pill, it becomes a horse pill. No further difference on horse pills themselves.
(in Repentance and Repentance+) Repentance
47 Shot Speed Down - 1 -0.15 shot speed. -0.30 shot speed.
48 Shot Speed Up + 1 +0.15 shot speed. +0.30 shot speed.
49 Experimental Pill N 3 Increases one attribute and decreases another randomly, with the same power as normal attribute up/down pills. Will not reduce any attributes if taken with Collectible Lucky Foot icon.pngLucky Foot, Collectible PHD icon.pngPHD or Collectible Virgo icon.pngVirgo. Will not increase any attribute if taken with Collectible False PHD icon.pngFalse PHD. If a pill-improving item is combined with False PHD, the pill gives an attribute increase, a decrease and a damage up. The two effects are doubled in power.

Pill Appearances

Normal Pills (in Repentance and Repentance+)Horse Pills
ID Appearance ID Appearance
5.70.1 BlueBlue.png 5.70.2049 Horse Pill Blue-Blue icon.png
5.70.2 WhiteBlue.png 5.70.2050 Horse Pill White-Blue icon.png
5.70.3 OrangeOrange.png 5.70.2051 Horse Pill Orange-Orange icon.png
5.70.4 Pill WhiteWhite.png 5.70.2052 Horse Pill White-White icon.png
5.70.5 RedSpecled.png 5.70.2053 Horse Pill Dots-Red icon.png
5.70.6 WhiteRed.png 5.70.2054 Horse Pill Pink-Red icon.png
5.70.7 BlueCyan.png 5.70.2055 Horse Pill Blue-Cadetblue icon.png
5.70.8 YellowOrange.png 5.70.2056 Horse Pill Yellow-Orange icon.png
5.70.9 SpottedwhiteWhite.png 5.70.2057 Horse Pill Dots-White icon.png
(except in Rebirth) Afterbirth
5.70.10 Pill White Cyan.png 5.70.2058 Horse Pill White-Azure icon.png
5.70.11 Pill Black Yellow.png 5.70.2059 Horse Pill Black-Yellow icon.png
5.70.12 Pill Black White.png 5.70.2060 Horse Pill White-Black icon.png
5.70.13 Pill White Yellow.png 5.70.2061 Horse Pill White-Yellow icon.png
(in Repentance and Repentance+) Repentance
5.70.14 Golden Pill icon.png 5.70.2062 Golden Horse Pill icon.png

(in Repentance and Repentance+) Pill Classes

Repentance introduces the mechanic of pill classes. Internally, pills are given a class from 0 to 3 and a polarity that reflects their influence:

Pills in class 0 have little to no impact on a run overall, while pills in higher classes are correspondingly more influential, class 3 pills having effects as significant as permanent stat changes. Classes that end with + or - denote a positive or negative effect, otherwise considered neutral.

This mechanic is used to balance the pill pool and avoid having too many negative or positive pills. Polarity is used by certain items to determine which pills to convert.

(in Repentance and Repentance+) Gold Pills

Repentance introduces Gold Pills (or Golden Pills). Using them will give a random pill effect. Gold pills only have a chance to be "used up" upon using them, which means that you can often use them many times before they finally disappear.

  • Unlocked by: Gold Pill Defeat Mega Satan as Character Tainted Cain icon.pngTainted Cain.
  • The possible effects are all effects that aren't in the run's pill pool, which means if you see an effect from a normal pill, you will never see it from a golden pill.
  • Items such as Collectible PHD icon.pngPHD or Collectible Lucky Foot icon.pngLucky Foot which alter pill effects also work on the effects of this pill, allowing many beneficial effects to be stacked with little risk. Effects altered by these items may overlap with the effects in the run's pill pool; for example, a run might have Tears Up in the pill pool and Tears Down outside of the pill pool, which will be turned into Tears Up due to the effects of the item.
  • Gold Pills have an ID of 5.70.14.
  • A Gold Pill can also be a Horse Pill. Golden Horse Pills use the Horse Pill effect on every use.
  • Golden horse pills are most likely the rarest pickup in the game with a 0.06% chance of spawning instead of a normal pill.
  • If a Golden Pill uses the 'Vurp' effect, and no other pill was used prior, another golden pill will drop.

(in Repentance and Repentance+) Horse Pills

Repentance introduces Horse Pills. These are larger versions of the standard pills with a more powerful effect, but only appear very rarely. Unique sound effects can be heard when they are used, and the narrator's normal spoken voice lines are instead shouted using a different voice.

  • Unlocked by: Horse Pill Defeat Mega Satan as Character Tainted Eve icon.pngTainted Eve.
  • All items that work with pills work identically with horse pills.
  • A horse pill with a given effect has the same color as the normal pill does.
  • Horse pills have an ID of the normal ID + 2048 (i.e. 1 << 11). For example, a white-blue pill has an ID of 2, so the horse pill version would have an ID of 5.70.2050.
  • It is also possible to have a golden horse pill. (It has an ID of 5.70.2062.)

Probabilities

Pills that spawn with a sub-type of 0 (i.e. a random pill) will have the following probabilities:

  • Random normal pill - 97.86%
  • Specific normal pill - 7.53%
  • Gold pill - 0.7%
  • Random horse pill - 1.43%
  • Specific horse pill - 0.11%
  • Gold horse pill - 0.01%

Notes

  • Among the attribute-modifying pill effects, only five of the seven visible attributes are covered: health, range, tears, speed, and luck. Both shot speed and damage can't be altered by pills.
    • (in Repentance and Repentance+) Shot speed can now be altered with pills. Damage can now also be altered with pills with Collectible False PHD icon.pngFalse PHD.
  • If a "Health Up" pill is used while Isaac has 11 empty red hearts and one non-red heart, the non-red heart will be replaced with an empty container, killing Isaac.
  • Having Collectible Midas' Touch icon.pngMidas' Touch, (except in Rebirth and Afterbirth)MeconiumMeconium, or (except in Rebirth and Afterbirth)Collectible Hallowed Ground icon.pngHallowed Ground and using a "Re-Lax" pill has a chance to spawn Golden Poop.pngGolden Poop, (except in Rebirth) Black Poop.pngBlack Poop, or (except in Rebirth and Afterbirth) White Poop.pngWhite Poop, respectively.
  • If the item Collectible PHD icon.pngPHD is picked up and then lost in any way, such as rerolling by the Collectible D4 icon.pngD4 or a Dice RoomDice Room, or dropping it as (in Repentance and Repentance+) Character Tainted Isaac icon.pngTainted Isaac, pills will remain fully identified for the rest of the run, but negative pills will not be converted.
  • (except in Rebirth) Pill effects have a chance to be narrated upon use, as do cards and runes.
  • (except in Rebirth) Currently, the "Retro Vision" pill effect can crash the game on some machines, resulting in restarting the current floor when the game is continued.
  • (except in Rebirth) The "Addicted!" pill will have no effect if Isaac has Collectible The Wafer icon.pngThe Wafer.
    • Despite this, if Isaac takes both the "Addicted!" pill with "Percs!" in the same room, a full heart of damage will be taken from all sources.
  • (except in Rebirth) Using an "Infested!" pill on Red Poop.pngRed Poop will spawn blue spiders and the red poop will regenerate.
  • (except in Rebirth) If a Tiny or Large Champion monster drops a "One Makes You Small"/"Larger" pill and either pill is not in the current pill pool, an existing pill will be overwritten. If the chosen pill was already identified, the new pill will also be.
  • (except in Rebirth) "R U A Wizard" does not affect Character Lilith icon.pngLilith's Incubus.
  • (except in Rebirth)Isaac's hitbox can be reduced to 30% of original, which is achieved after 6 One Makes You Small pills. Further pills will only make him visually smaller, with no additional benefit.
  • (except in Rebirth and Afterbirth) Using a "Gulp!" pill while holding two trinkets (with (except in Rebirth and Afterbirth)Collectible Belly Button icon.pngBelly Button or Collectible Mom's Purse icon.pngMom's Purse) will cause both trinkets to be absorbed.
  • Character Magdalene icon.pngMagdalene's starting pill will override one of the pills in the current run's pill set if it doesn't exist in it ("Speed Up" for Afterbirth+, or "Full Health" in Repentance). The pill that is converted is dependent on the run's seed.
    • This only applies if the run is started as Magdalene, not if Isaac turns into Magdalene using (except in Rebirth and Afterbirth)Collectible Clicker icon.pngClicker.
  • (in Repentance and Repentance+) All golden pills in the run have a shared sequence of effects they activate, so reversing the effects of one golden pill through (except in Rebirth)Collectible Glowing Hourglass icon.pngGlowing Hourglass and consuming another golden pill will activate the same effects.
  • (in Repentance and Repentance+) If a "Vurp!" effect is activated by a golden pill, it will spawn the last non-golden pill taken by Isaac, or a golden pill if no non-golden pills have been taken by Isaac in the run.
  • (in Repentance and Repentance+) If a Marked Skull is destroyed while Isaac is holding Collectible Little Baggy icon.pngLittle Baggy, it will spawn a "Telepill" instead of 0 - The Fool0 - The Fool. If "Telepills" doesn't exist in the current run's pill set, an existing pill will be overwritten. The pill that is converted is dependent on the run's seed.
  • (in Repentance and Repentance+) While transformed into Character The Lost icon.pngThe Lost by a White Fireplace, "Health Down" pills turn into "Health Up" pills, regardless of Isaac's number of red heart containers.
  • (in Repentance+) The "Amnesia" and "???" pills are unobtainable in Greed Mode.

Strategy

  • (in Repentance and Repentance+) There are 24 good effects, 14 neutral (sometimes good/sometimes bad) effects, and 12 negative effects. This means that taking mystery pills is usually beneficial.
  • Use of unidentified pills is recommended for outside of combat as Hematemesis, R U a Wizard?, Paralysis, (except in Rebirth)Addicted!, (except in Rebirth and Afterbirth) X-Lax, and (except in Rebirth and Afterbirth) I'm Excited!!! can be detrimental mid-fight. However, (except in Rebirth and Afterbirth) I'm Drowsy..., (except in Rebirth and Afterbirth) Something's wrong..., Lemon Party, Bad Gas, and Pheromones are useless outside of combat.
  • (except in Rebirth) Percs! can be used in the Sacrifice RoomSacrifice Room to reduce the damage Isaac takes, potentially allowing him to do more sacrifices. However, if Isaac is teleported to the Devil/Angel room, he loses the effect.
  • (except in Rebirth) The invincibility effect from Power Pill and (except in Rebirth and Afterbirth) Feels like I'm walking on sunshine! can be utilized to get into Curse RoomCurse Rooms, play Blood Donation Machine.pngBlood Donation Machines and (in Repentance and Repentance+) Confessional.pngConfessionals, or use Devil Beggar.pngDevil Beggars and (in Repentance and Repentance+) Hell Game.pngHell Games without taking any damage.
    • (except in Rebirth) Percs! can be used to reduce damage from these from chapter 4 onward.
  • (in Repentance and Repentance+)Endless NamelessEndless Nameless can be used to effectively generate infinite golden pills, as the trinket's ability to respawn collectibles applies with every use.
  • (in Repentance and Repentance+) Taking only golden pills in a run can allow for infinite golden pill generation by repeatedly activating the Vurp! effect.

Unlockable Achievements

Trivia

  • (except in Rebirth and Afterbirth) The Vurp! pill is a portmanteau of the words vomit and burp.
  • (except in Rebirth) Power Pills activating the Gamekid effect is a reference to Pac-Man, in which the "Super-Pac" powerup is obtained by eating a Power Pellet.
  • "I Found Pills (and Ate Them)," "R U a Wizard?," and "I can see Forever" are all image macro memes.
  • (except in Rebirth and Afterbirth) The Feels like I'm walking on sunshine! pill is a reference to the 80s song Walking on Sunshine.
    • Furthermore, creator Edmund McMillen made in 2010 a video with the same name, although it doesn't feature the actual Walking on Sunshine song.
  • Balls of Steel is a reference to Duke Nukem; it is one of Duke's more famous quotes.
  • Explosive Diarrhea is extremely loud and forceful diarrhea. In the original game, the message that displayed when the pill was activated was "Oh No!". The pill name and effect are likely a reference to Atomic Bomberman where a pickup of the same name would cause the player to drop bombs behind them uncontrollably for a short duration.
  • Shot speed effects were introduced in The Binding of Isaac: Eternal Edition, after the release of Rebirth. They were finally added to Rebirth in the Repentance DLC.
  • Hematemesis is a medical term for vomiting blood.
  • Lemon Party is a reference to internet shock site featuring a group of elderly men performing oral sex, peeing on each other.
  • "Puberty" having a negative sound effect is a tongue in cheek connotation to how unpleasant that period in life can be.
  • (except in Rebirth) Friends Till the End! was originally in the Wrath of the Lamb but removed in Rebirth, then put back into Afterbirth.
  • (in Afterbirth) Friends Till The End! is the only non-narrated pill.
  • 48 Hour Energy is a reference to the drink 5 Hour Energy.
  • (except in Rebirth and Afterbirth) X-Lax is a reference to the anti-constipation medicine Ex-Lax.
  • (except in Rebirth) "One makes you larger" and "One makes you small" are references to Alice in Wonderland, and the specific wording is a reference to the song White Rabbit by Jefferson Airplane.
  • (except in Rebirth) "Percs" is a reference to a street name for the prescription drug Percocet, which is more generically known as Oxycodone. This drug is meant to be used to treat pain, but it is often abused for recreational purposes.
  • (except in Rebirth) The "???" is the only pill that has 3 different narrated voice lines.
  • (in Repentance and Repentance+) "Horse pills" is a slang term used to refer to large, hard to swallow pills, hence their sprites being larger than those of regular pills.

Voiceovers

Pill Voiceover (Standard Pills) Voiceover (Horse Pills)
???
48 Hour Energy
Addicted
Amnesia
Bad Gas
Bad Trip
Balls of Steel
Bombs Are Key
Experimental Pill
Explosive Diarrhea
Feels like I'm walking on sunshine!
Friends Till the End!
Full Health
Gulp!
Health Down
Health Up
Hematemesis
Horf!
I Can See Forever
I Found Pills
I'm Drowsy...
I'm Excited!!!
Infested!
Infested?
Lemon Party
Luck Down
Luck Up
One Makes You Larger
One Makes You Small
Paralysis
Percs
Pheromones
Power Pill
Pretty Fly
Puberty
R U a Wizard?
Range Down
Range Up
Re-Lax
Retro Vision
Shot Speed Down
Shot Speed Up
Something's wrong...
Speed Down
Speed Up
Tears Down
Tears Up
Telepills
Vurp!
X-Lax

Gallery

Bugs

Bug Bug! (except in Rebirth) Any blue flies and blue spiders created by pill effects can be multiplied when Collectible Glowing Hourglass icon.pngGlowing Hourglass teleports Isaac in a way that does not move him to a different room from the one he is currently in (such as by teleporting to the previous room then using it again).