The Binding of Isaac Rebirth: All Challenges Guide

Challenges 1, 2, 3, 12, 13, 14, 15, 16, 17 and 18 are all unlocked by default and do not require any unlocking. Every challenge you beat unlocks an item on that save file. For example challenge 17: ‘Waka Waka’ unlocks the item death’s touch which turns Isaac’s tears into powerful scythes.

To unlock challenge 4: ‘Darkness Falls’ you need to defeat Isaac while playing as Eve. To unlock Eve simply beat two floors in a row without picking up hearts. To fight Isaac you need to go up the light after defeating it lives or the angel room after Mum’s heart. The goal of the challenge is to beat Satan. Beating Challenge 4 unlocks the rune of Dagaz.

To unlock challenge 5: ‘The Tank’ and challenge 10: ‘Cursed’ You need to have seven red heart containers at one time. This also unlocks Magdalene, a solid character with extra health. Your goal is to reach and defeat Mum. Beating challenge 5 unlocks the rune of Ansuz. Beating challenge 10 unlocks the item credit card

To unlock challenge 6: ‘Solar System’ you need to defeat Mum’s heart three times. The goal of this challenge is to beat mum’s heart / It lives. Challenge 6 unlocks the rune of Perthro.

To unlock challenge 7: ‘Suicide King’ You must defeat Mum’s heart 11 times. Beating Mum’s heart 11 times also unlocks it lives, the boss which replaces Mum’s heart. Your goal is to defeat
Isaac. Challenge 7 unlocks the item Suicide king.

To unlock challenge 8: ‘Cat Got Your Tongue’ You need to become Guppy. To transform into Guppy You must collect any three of the following items: Guppy’s head, Guppy’s tail, Guppy’s paw, Guppy’s hair ball, Guppy’s collar or dead cat. Your goal is to defeat Mum. Challenge 8 unlocks the rune of Algiz.

To unlock challenge 9: ‘Demo man’ You need to defeat mum’s heart 9 times. The goal of this challenge is mum’s heart / It lives. Challenge 9 unlocks the item chaos card.

To unlock challenge 11: ‘Glass cannon’ you need to beat challenge 19 and defeat Lokii, a boss found in the womb. The goal is to beat Satan. Challenge 11 unlocks the item rules card.

To unlock challenge 19: ‘Family man’ You need to collect both key pieces from blowing up the angel statues in the angel room in 1 run. However, You cant blow up the statues until you beat the lamb or ???, Only then can you do this. Your goal is to beat Isaac. Challenge 19 unlocks the item epic fetus.

To unlock challenge 20: ‘Purist’ You need to defeat Mum. The goal of this challenge is to beat mum’s heart / It lives. Challenge 20 unlocks the rune of Berkano.

This is all of the challenges in rebirth.

The Afterbirth DLC to Isaac adds 10 new challenges to the binding of Isaac challenge list, many of these have different rules only in these challenges and some use the new items in the DLC.
Most of these challenges in the DLC are unlocked by beating Mum, those challenges are: Challenge 21, challenge 22, challenge 25, challenge 28, challenge 29 and challenge 30.

To unlock challenge 23: ‘Blue Bomber’ You need to destroy 10 tinted rocks and defeat Mum’s heart 11 times. Tinted rocks are slightly blue tinted colour rocks that can give a soul heart, they also have a small cross on them. The goal for this challenge is to beat Satan. Challenge 23 unlocks Gold bombs.

To unlock challenge 24: ‘Pay To Play’ you must defeat Isaac as Cain. The goal is Isaac and beating challenge 24 unlocks 2 new pills.

To unlock challenge 26: ‘I Rule!’ You must defeat ???, the Lamb and Satan as Isaac. The goal of this challenge is to defeat Mega Satan. The door to Mega Satan is found in dark room or the chest in the starting room. To enter you need dads key or both key pieces from the angels. Challenge 26 unlocks the item poker chip.

To unlock challenge 27: ‘Brains!’ You need to defeat Issac 5 times. The goal of this challenge is ???.
You play as ??? when you start this challenge. Challenge 27 unlocks the item stud finder.

These are all the added challenges in afterbirth.

Afterbirth plus adds 5 new challenges to the game. Challenge 32 requires you to beat Mum.

To unlock challenge 31: ‘Backasswords’ You need to defeat either the lamb or ???. The goal of this challenge is to reach basement, cellar or burning basement. This challenge starts at mega Satan and you work your way backwards.

To unlock challenge 33: ‘Pokey mans’ you need to defeat Mum’s heart 11 times. Your goal is to beat Isaac.

To unlock challenge 34: ‘Ultra Hard’ You need to defeat The lamb or ???, You must do this through the Polaroid or negative and not through the sacrifice room. Your goal is Mega Satan.

To unlock challenge 35: ‘Pong’ You need to defeat Isaac 5 times. Your goal is ???. This challenge is intended to be done after challenge 34 but you can do it before if you unlock it before challenge 34.

These are all the challenges in Afterbirth plus.