At the start of each run, an effect is randomly assigned to each color of the pill. The pill effect for that color will remain constant throughout the run. (However, it is possible for PHD or Virgo to reassign some of the effects, such that 2 different colored pills will have the same effect). Pills will start the game unidentified (unless the player is holding 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.
- The pill pool for each run has increased from 9 to 13.
|0||Bad Gas||Isaac farts, poisoning enemies around him.|
|1||Bad Trip||Injures Isaac by a full heart. If a Bad Trip pill is used while Isaac only has a single heart left or less, the pill will turn into a Full Health pill instead. (This damage counts as red heart damage to get a Devil Deal.)|
|2||Balls of Steel||Grants Isaac two soul hearts.|
|3||Bombs Are Key||Swaps the values of Isaac's bombs and keys.|
|4||Explosive Diarrhea||Spawns five active bombs behind Isaac over a period of five seconds, at one a second.|
|5||Full Health||Refills every empty red heart container.|
|6||Health Down||Removes one red heart container upon use. While Isaac has one or fewer red heart containers, it will act as a Health Up pill instead. ??? can encounter Health Down pills, even though he can't have red heart containers.|
|7||Health Up||Adds one empty red heart container upon use.|
|8||I Found Pills||Changes the appearance of Isaac's face. This pill is cosmetic only, , and the effect disappears when you leave the room.|
|9||Puberty||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.|
Consuming three puberty pills will grant the Adult transformation, granting one red heart container (one time effect).
|10||Pretty Fly||Grants 1 fly orbital that circles the player, blocking projectiles and damaging fly-type enemies on touch.|
|11||Range Down||Decreases Isaac's range by 2.|
|12||Range Up||Increases Isaac's range by 2.5.|
|13||Speed Down||Decreases Isaac's movement speed by 0.12.|
|14||Speed Up||Increases Isaac's movement speed by 0.15.|
|15||Tears Down||Decreases Isaac's tears by 0.28.|
|16||Tears Up||Increases Isaac's tears by 0.35.|
|17||Luck Down||Decreases Isaac's luck by 1.|
|18||Luck Up||Increases Isaac's luck by 1.|
|19||Telepills||Isaac gets teleported to a random room. Has a small chance to teleport Isaac to the I AM ERROR room, and an extremely small chance to teleport him to the Black Market, like Undefined. Unobtainable in Greed Mode.|
|20||48 Hour Energy||Drops one to two little batteries and fully charges the spacebar item. Can be used with the Placebo or D1 to generate infinite batteries.|
|21||Hematemesis||Empties all but one red heart container and spawns 1-4 red hearts. If Isaac only has half of a heart left, it will heal him to one heart. If used without any red heart containers, no health will be deducted, but red hearts will still spawn. If used in a black heart or eternal heart-containing super secret room, it will spawn those types of hearts instead.|
|22||Paralysis||Prevents Isaac from moving and shooting for 2 seconds.|
|23||I can see forever!||Opens all entrances to the secret room and super secret room for the current floor.|
|24||Pheromones||Charms all enemies in the room for a short period of time.|
|25||Amnesia||Replaces the floor map with a ? for the rest of the floor. 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 cannot be negated by Black Candle. Also the only pill to have its flavor text appear on a piece of paper as curses do.|
|26||Lemon Party||Spawns a large yellow pool (similar to Lemon Mishap) around your character. Greatly damages any enemy that steps on it, for 22 damage per tick or 66 damage per second.|
|27||R U a Wizard?||Tears are shot diagonally outwards for about 30 seconds. This effect does not reset upon exiting the room.|
|28||Percs!||Gives The Wafer effect while in the room : reduces all damage taken to half a heart.|
Unlocked by completing Challenge #24: PAY TO PLAY.
|29||Addicted!||Makes Isaac take a full heart of damage from all sources for the current room. Also changes his appearance for the room.|
Unlocked by completing Challenge #24: PAY TO PLAY.
|30||Re-Lax||For a short time, poop spawns wherever Isaac moves, like Explosive Diarrhea but with poop. A higher move speed means you can touch more tiles in the same time. A pun on laxatives.|
Unlocked by completing Challenge #25: Have a Heart.
|31||???||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 cannot be negated by Black Candle. 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 completing Challenge #25: Have a Heart.
|32||One makes you larger||Increases Isaac's size and decreases the pitch of his voice. This effect does not increase the size of Isaac's hitbox but will increase the size of The Forgotten's bone club. These pills contribute to the Stompy transformation.|
|33||One makes you small||Decreases Isaac's size and increases the pitch of his voice. This effect decreases the size of Isaac's hitbox.|
|34||Infested!||Destroys all poop in the room and spawns a single blue spider under Isaac and on each destroyed poop.|
|35||Infested?||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.|
|36||Power Pill!||Temporarily grants invulnerability, inflicts fear on enemies in the room, and lets Isaac deal contact damage, similar to The Gamekid.|
|37||Retro Vision||Pixelates the screen 3 times over 30 seconds. The effect continues between floors.|
|38||Friends Till The End!||Spawns three blue flies.|
|39||X-Lax||Creates a pool of slippery brown creep underneath Isaac.|
|40||Something's wrong...||Creates a pool of black creep beneath Isaac that slows enemies.|
|41||I'm Drowsy...||Slows all enemies for the duration of the room.|
|42||I'm Excited!!!||Increases the speed of all enemies for the duration of the room. The effect triggers again 30 seconds after use and 60 seconds after use.|
|43||Gulp!||Any trinkets that the player is holding are destroyed, and their effects are permanently applied to the player.|
Unlocked by acquiring the Once More With Feeling! achievement.
|44||Horf!||Isaac shoots an explosive tear with the Ipecac effect that always deals 200 damage.|
Unlocked by acquiring the Dedication achievement.
|45||Feels like I'm walking on sunshine!||Temporarily makes Isaac invincible, similar to Unicorn Stump.|
Unlocked by acquiring the Sin Collector achievement.
|46||Vurp!||Throws up the last pill you used. Will spawn itself if no other pills were taken beforehand.|
Unlocked by acquiring the U Broke It! achievement.
- 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.
- Pill effects have a chance to be narrated upon use, as do cards and runes.
- Currently, the "Retro Vision" pill effect can crash the game on some machines, resulting in restarting the current floor when the game is continued.
- The "Addicted!" pill will have no effect if Isaac has The Wafer.
- Despite this, if one takes both the "Addicted!" pill with "Percs!" in the same room, Isaac will take a full heart of damage from all sources.
- Having Midas' Touch, Meconium, or Hallowed Ground and using a "Re-Lax" pill has a chance to spawn golden poop, black poop, or white poop, respectively.
- Using an "Infested!" pill on red poop will spawn blue spiders and the red poop will regenerate.
- 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.
- "R U A Wizard" does not affect Lilith's Incubus.
- Using a "Gulp!" pill while holding two trinkets (with Belly Button or Mom's Purse) will cause both trinkets to be absorbed.
- 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.
- Use of unidentified pills is recommended for outside of combat as Hematemesis, R U a Wizard?, Paralysis, Addicted!, X-Lax, and I'm Excited!!! can be detrimental mid-fight. However, I'm Drowsy..., Something's wrong..., Lemon Party, Bad Gas, and Pheromones are useless outside of combat.
- Percs! can be used in the sacrifice 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.
- The invincibility effect from Power Pill and Feels like I'm walking on sunshine! can be utilized to get into curse rooms, play blood donation machines, or use Devil beggars without taking any damage.
- Percs! can be used to reduce damage from these from chapter 4 onward.
- Lachryphagy - Collect 10 "tears up" items or pills in one run.
- Lemon Party is an internet shock site featuring a group of elderly men performing oral sex.
- The Vurp! pill is a portmanteau of the words vomit and burp.
- 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.
- Despite being called I Can See Forever, the effects only last for the rest of that floor.
- The Feels like I'm walking on sunshine! pill is a reference to the 80s song Walking on Sunshine.
- 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.
- Friends Till the End! was originally in the Wrath of the Lamb but removed in Rebirth, then put back into Afterbirth.
- Friends Till The End! is the only non-narrated pill.
- 48 Hour Energy is a reference to the drink 5 Hour Energy.
- X-Lax is a reference to the anti-constipation medicine Ex-Lax.
- "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.
- "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.
- The "???" is the only pill that has 3 different narrated voice lines.
|48 Hour Energy|
|Balls of Steel|
|Bombs Are Key|
|Feels like I'm walking on sunshine!|
|Friends Till the End!|
|I Can See Forever|
|I Found Pills|
|One Makes You Larger|
|One Makes You Small|
|R U a Wizard?|
|The Binding of Isaac: Rebirth|
|Achievements||Attributes||Bosses||Cards and Runes||Challenges||Chapters|