Challenges

Challenges are unique runs in the game. Challenges typically start the player off with one or more specific items which make normal play more difficult. You will not find Treasure Rooms (with the exception of a select few challenges). Completing one of the thirty five challenges unlocks new content for the game, such as Runes.

General Strategy

Most challenges are geared to make a run difficult in some form. Sometimes, these challenges are easy, like Computer Savvy. Other times, they can be vicious, like Solar System. Each challenge has a certain strategy that can make the run easier. However, there are a few strategies that can apply to all challenges.

• You can play in co-op for every challenge, making it easier for the ones where you cannot fire tears - especially for Cat Got Your Tongue, since it will spawn flies.
• Because of the lack of Treasure Rooms, Devil Rooms become much more valuable. Some challenges can be made much easier by making just one deal.
  
• You can also be more liberal with your use of keys for the same reason. Trinkets and Items that generate more coins, along with upgraded shops, can help reduce the difficulty in many challenge runs.
• The Bible can make the end of some runs extremely easy. Because of how some challenges operate, the run may only require defeating Mom or Mom's Heart / It Lives. Since The Bible is a one-hit kill against these, getting it when you have the chance is usually a good investment for these runs.
  
  • Pandora's Box will spawn The Bible if used in Womb II, Utero II, or Scarred Womb II, which may then be used against Mom's Heart / It Lives.
• Curse Rooms gain value since they can spawn items. You may wish to restart on the first floor until your Curse Room spawns an item worth 1 heart of damage.
• Dice Rooms and the D4 are very useful, as in some cases you can reroll your entire build and remove (or add) difficulty.
  • Dice rooms do not re-roll starter challenge items or remove Blindfolded.
  • Butter! can remove starter items.
• In Blindfolded challenges, familiars can make the run easier, as they are your only source of conventional damage. Powerful familiars like Daddy Longlegs, Lil Brimstone, and Incubus are very good items to pick up. Some of the strongest familiars need to be unlocked first, so it may be wise to take the time to unlock them beforehand.
  • The Boomerang, The Candle, and Red Candle are also useful for blindfolded challenges, since they deal damage and recharge based on a timer.
    • In Blindfolded challenges, if possible finding and using the Clicker, change yourself into the character Lilith, will make these challenges incredibly easy with access to tears through her Incubus you gain.

• In challenges that remove Treasure Rooms, Chaos has more potential to be useful by potentially making Treasure Room (among other rare items) items purchasable from the shop. On the downside, it may replace the Devil/Angel Room items with something less valuable.
• Defeating a boss beyond the specified end of the challenge (e.g. defeating Mom's Heart when the goal is to defeat Mom) will still cause them to drop the trophy.
  • This means a legitimate tactic for some of the longer challenges (e.g. XXXXXXXXL) is to use the Sacrifice Room until it teleports you to the Dark Room, then going through and defeating The Lamb, completing the challenge regardless of what floor you were teleported from.

Notes

• New content, other than the Challenge Reward, cannot be unlocked. Likewise, you will not find a Donation Machine anywhere.
• The Challenge reward will not be unlocked unless you pick up the trophy, meaning that if a Devil Room or Angel Room appears and allows you to go to Sheol or the Cathedral, you will be forfeiting the unlock if you fail to complete the floor.
• Any challenge featuring Isaac will not start with The D6.

Challenge list

Name	Conditions	Goal	Unlocked by	Unlocks
1. Pitch Black	Curse of Darkness Curse of the Unknown : yes : no		Default	Rune of Hagalaz
2. High Brow	Starts with: Number One E Coli Butt Bombs Flush! Petrified Poop : no : yes		Default	Rune of Jera
3. Head Trauma	Starts with: Tiny Planet Soy Milk The Small Rock Iron Bar : no : yes		Default	Rune of Ehwaz
4. Darkness Falls	Starts with: Pentagram Dead Bird Whore of Babylon Razor Blade Sacrificial Dagger Dark Matter : no : yes		Defeat Mom's Heart 11 times	Rune of Dagaz
5. The Tank	Starts with: Infamy Bucket of Lard Thunder Thighs Yum Heart : no : yes		Have 7 or more heart containers at one time	Rune of Ansuz
6. Solar System	Blindfolded Starts with: Distant Admiration Forever Alone Halo of Flies Transcendence : no : yes	/	Defeat Mom's Heart 3 times	Rune of Perthro
7. Suicide King	Starts with: Ipecac Mr. Mega My Reflection 1 random Pill : no : yes		Defeat Mom's Heart 11 times	Suicide King
8. Cat Got Your Tongue	Blindfolded Starts with: Guppy's Hair Ball Guppy's Head Guppy's Tail : no : yes		Become Guppy (Collect 3 Guppy Items)	Rune of Algiz
9. Demo Man	Starts with: Dr. Fetus Remote Detonator Match Stick : no : yes	/	Defeat Mom's Heart 9 times	Chaos Card
10. Cursed!	Starts with: Blue Map The Compass Raw Liver Treasure Map Yum Heart Child's Heart Curse of the Cursed : yes : yes		Have 7 or more heart containers at one time	Credit Card
11. Glass Cannon	Starts with: Epic Fetus Loki's Horns : no : yes		Beat challenge #19 and defeat Lokii for the 1st time	Rules Card
12. When Life Gives You Lemons	Starts with: 9 Volt Habit Lemon Mishap 1 Lemon Party pill : no : yes		Default	Card Against Humanity
13. Beans!	Blindfolded Starts with: 9 Volt The Bean The Black Bean Butt Bombs Pyro : no : yes		Default	Burnt Penny
14. It's in the Cards	Starts with: 9 Volt The Battery Deck of Cards Starter Deck 2 random tarot cards : no : yes		Default	SMB Super Fan
15. Slow Roll	Starts with: Cupid's Arrow My Reflection Polyphemus : no : yes		Default	Swallowed Penny
16. Computer Savvy	Starts with: Spoon Bender Technology Technology 2 : no : yes		Default	Robo-Baby 2.0
17. Waka Waka	Starts with: Anti-Gravity Strange Attractor : no : yes		Default	Death's Touch
18. The Host	Starts with: The Mulligan Spider Baby Tick : no : yes		Default	Technology .5
19. The Family Man	Blindfolded Starts with: BFFS! Brother Bobby Dad's Key Rotten Baby Sister Maggy : no : yes		Pick up both Key pieces from the Angels in one run	Epic Fetus
20. Purist	: no : yes	/	Defeat Mom for the first time	Rune of Berkano
21. XXXXXXXXL	: yes : yes Every floor is the size of an XL Womb floor, but does not combine the floors of each chapter.	/	Defeat Mom for the 1st time	Gold Heart
22. SPEED!	: yes : yes Everything is sped up like the Broken Watch effect.	/ within 16 minutes, otherwise under constant periodic damage every 10 seconds.	Defeat Mom for the 1st time	Get out of Jail Free Card
23. Blue Bomber	Blindfolded Starts with: Brother Bobby Kamikaze! Pyromaniac Mr. Mega : no : yes		Destroy 10 tinted rocks and defeat Mom's Heart 11 times	Gold Bomb
24. PAY TO PLAY	Starts with: Money = Power Sack of Pennies 50 coins : no : yes Every door costs 1 cent to enter. Isaac drops money when hit. Isaac dies if you run out of money.		Defeat Isaac as Cain	2 new pills
25. Have a Heart	Starts with: Charm of the Vampire : yes : yes Pennies drop instead of red hearts. Many items that restore red hearts have no effect.	/	Defeat Mom for the 1st time	2 new pills 2
26. I RULE!	Starts with: The Boomerang Key Piece 1 Key Piece 2 The Ladder Mom's Knife Trinity Shield : no : yes		Defeat ??? or The Lamb for the 1st time	Poker Chip
27. BRAINS!	Blindfolded Starts with: 3 Bob's Brain Thunder Thighs : no : yes		Defeat Isaac 5 times	Stud Finder
28. PRIDE DAY!	Starts with: 3 Dollar Bill Rainbow Baby Rainbow Worm : no : yes Cannot drop or replace Rainbow Worm.	/	Defeat Mom for the 1st time	D8
29. Onan's Streak	Starts with: The Book of Belial Chocolate Milk : yes : yes Missing a shot deals damage to Judas.		Defeat Mom for the 1st time	Kidney Stone
30. The Guardian	Blindfolded Starts with: Holy Grail Isaac's Heart Punching Bag Spear of Destiny : no : yes Isaac's Heart will follow the Punching Bag instead of Isaac.	/	Defeat Mom for the 1st time	Blank Rune
31. Backasswards	Starts with: 8-10 random items : no : yes All Chapters progress in reverse order, losing 1 item and 1 red heart container each floor you ascend.	The Basement/The Cellar/Burning Basement I	Defeat ??? or The Lamb for the 1st time	Laz Bleeds More!
32. Aprils Fool	: yes : yes The minimap displays the floor's layout accurately, but displays Isaac's position inaccurately. Pedestal items and pickups are not what they appear to be. Active item, pill, card, and rune effects are randomized upon each use, making them very unreliable or deadly (for example Suicide King). Items with no charge time (i.e. How To Jump, IV Bag, etc) can be used repeatedly for random effects. Trinkets function normally. Every boss is The Bloat. Isaac's health is not what it appears to be. Key and bomb numbers are accurate.	/	Defeat Mom for the 1st time	Maggy Now Holds a Pill!
33. Pokey Mans	Starts with: Friendly Ball Mom's Eyeshadow : no : yes Each use of Friendly Ball causes a random monster to be spawned. Friendly Ball instantly charges once the spawned monster is killed.		Defeat Mom's Heart 11 times	Charged Key
34. Ultra Hard	Starts with: Key Piece 1 Key Piece 2 Curse of the Labyrinth Curse of the Blind Curse of the Lost Curse of the Maze : yes : yes All enemies spawn as champions if possible. Boss fights will be double trouble if possible. No heart pickups drop.		Defeat ??? or The Lamb for the first time	Samson Feels Healthy!
35. Pong	Starts with: Cupid's Arrow Rubber Cement : no : yes Damage fixed at 100, tear delay fixed at 150.		Defeat Isaac 5 times	Greed's Gullet

Challenges

Rebirth
1.	Pitch Black	2.	High Brow	3.	Head Trauma	4.	Darkness Falls	5.	The Tank	6.	Solar System	7.	Suicide King	8.	Cat Got Your Tongue
9.	Demo Man	10.	Cursed!	11.	Glass Cannon	12.	When Life Gives You Lemons	13.	Beans!	14.	It's in the Cards	15.	Slow Roll	16.	Computer Savvy
17.	Waka Waka	18.	The Host	19.	The Family Man	20.	Purist
Afterbirth
21.	XXXXXXXXL	22.	SPEED!	23.	Blue Bomber	24.	PAY TO PLAY	25.	Have a Heart	26.	I RULE!	27.	BRAINS!	28.	PRIDE DAY!
29.	Onan's Streak	30.	The Guardian
Afterbirth †
31.	Backasswards	32.	Aprils Fool	33.	Pokey Mans	34.	Ultra Hard	35.	Pong