Most of the challenges, especially the ones included in Afterbirth, qualify as this. Notable offenders include:
- Most challenges where you're blindfolded and thus unable to fire tears falls into this category, like "Cat Got Your Tongue" (rely only on flies and Guppy's Hairball for damage). Other examples include:
- The Solar System challenge. It limits you to using fly orbitals, fly enemies, and bombs to attack enemies. This alone wouldn’t be too bad if not for the sheer number of enemies that either fire or charge at you when you get too close with no telegraph making avoiding damage nearly impossible. Your goal is Mom’s Heart/It Lives and the Womb is choke full of such enemies.
- The Family Man challenge is probably the hardest of the base game. Your only means of damage are through three familiars. Thankfully, one of them is Rotten Baby, which scales with your damage. Otherwise however, you're gonna have a very hard time trying to damage enemies even slightly. It's borderline impossible to complete the challenge without resorting to resetting until you can get a Cube of Meat or Ball of Bandages on the first floor. Repentance alleviated the challenge marginally as Brother Bobby and Sister Maggy received buffs, but it's still a tough experience.
- The Brains! challenge in Afterbirth. During it, your only offensive weapons are three Bob's Brains, which is a Scrappy Weapon infamous for its tendency to blow up right in your face. What makes this worse is that you're playing as ???/Blue Baby, making it more difficult to recover health, and you have to fight all the way to the Chest.
- The Suicide King challenge in Rebirth tasks you with defeating Isaac as Lazarus. The catch? You have My Reflection and Ipecac equipped for the entire run. Have fun playing the entire game with exploding tears that boomerang right back in your face!
- The Speed! challenge in Afterbirth. Enemy movement and bullet speed are dialed up significantly while you start as basic Isaac. There's Treasure Rooms, but that's little comfort when bosses like Gurdy Jr. can move twice as fast and become practically unavoidable. Also, if you don't finish all the way to It Lives in under 16 minutes, you get half a heart of damage every few seconds which can kill you! It goes to the point it's almost impossible to even beat the first floor if you get a hard boss unless you get a good start
. It's basically saying "reload until you get Brimstone or something else that kill instantly, otherwise you lose." A patch eventually increased Isaac's movement speed too, making the challenge slightly more manageable in that you'll at least be able to outrun most enemies that chase you. - The Guardian challenge from Afterbirth. You must protect Isaac's Heart which isn't following you, but rather the Punching Bag that wanders around the room. Also, the Punching Bag is the one that takes damage, not the heart. You have no real control over whether or not you take damage, as all enemies attack the Punching Bag rather than you. Hazards like red poop and spikes turn the challenge into a Luck-Based Mission because, if the Punching Bag touches a hazard just once, you lose many hearts instantly! Repentance throws a few small bones your way, with the buffs to Isaac's Heart letting you deal collision damage to enemies, and giving the heart a way to fight back.
- While it's really hard to actually die in the Aprils Fool challengenote , it still obviously wants to troll the player. You're playing as basic Isaac while your map doesn't work properly and Stonies can be replaced by Cross Stonies (their more dangerous counterpart). What makes it infamous, however, is The Bloat; you have to fight him on every floor. Yes, even in the early-game when you're less likely to have good items to deal with him. Pickups can also become red hearts when your health is full, thus rendering them useless, and coins are harder to collect. This is because during the challenge all trinkets, pickups, and items' sprites are displayed incorrectly. Depending on your luck, that'll be a blessing in disguise or a further hinderance. If it's the former, however, this challenge can be cheesed.
- The Ultra Hard challenge in Afterbirth+ lives up to its name. You are Isaac (minus the D6) stuck with Curse of the Lost, Curse of the Maze, Curse of the Blind, and Curse of the Labyrinth with the possibility of additional curses too. The four permanent curses furthermore cannot be dispelled with the Black Candle or Dagaz Rune. All enemies and bosses that have Champion variants will be Champions, no exceptions. What's worse is that the challenge will never drop hearts - ever. The only way to get health is to get HP Ups, items that directly give you health (items that drop hearts on the ground do not work), or get a regenerating item ala Placenta or Blood Leech. What's worse is that the end goal is beating Mega Satan, which sets up a long and frustrating road, and the Ehwaz Rune doesn't work, so you can't skip any floors either. Your reward for all that effort? Samson starts with the Child's Heart trinket. While it's a handy trinket for someone like Samson, it's definitely not worth the struggle.
- Unlocking the final character of the Afterbirth+ expansion (the Forgotten) is this, besides being also a Guide Dang It!. For starters, you must beat the first boss in under a minute, which is practically a Luck-Based Mission. Then, you must go back to the first room and bomb the center; this will make the Broken Shovel appear, which has the nasty effect of making Mom's feet appear nonstop every couple of seconds and try to attack you (although you can "use" the Shovel to neutralize the effect every fourth room). You must then try and survive the next five floors and defeat Mom without getting stomped into red paste, enter the Boss Rush, and defeat that (mercifully, the Broken Shovel opens the Boss Rush, even if you took longer than 20 minutes). After that, the Broken Shovel becomes the non-cursed Mom's Shovel, and it's "just" a matter of reaching the Dark Room floor and digging up a mound of dirt. And no, you cannot swap the Broken Shovel out for another active item and then come back for it later, because it disappears if you do.
- The "Backasswards" challenge requires you to start from Mega Satan and fight your way back to the Basement. You start with a full loadout of items, and as you progress, you lose items at random. Sounds easy on paper, but it's much more difficult in practice. For starters, you have to beat Mega Satan and regular Satan back-to-back. Your starting loadout is randomized and may not offer any decent synergies, especially since you only get ten as opposed to the 15+ you'd likely get a on a normal run at that point. Mega Satan is a notorious Damage Sponge and Bullet Hell boss and spawns waves of Degraded Bosses, making it hard to outlast without significant damage. Since your items disappear one-by-one on each floor you enter, if you do manage to get a powerful combo that can beat Mega Satan pretty fast (or something like Gnawed Leaf and an item that can do damage without moving), there's a decent chance one of those items will disappear, potentially screwing you over for the ensuing Satan fight. Fortunately, that's the biggest hurdle of the challenge, so passing it means you'll likely be able to get through the rest of the floors without too much trouble.
- The "Bloody Mary" challenge. You start as Bethany with Book of Belial instead of Virtues, Anemic, Blood Bag for extra starting health and speed, Child's Heart to increase red heart spawns, and there's no treasure rooms. Doesn't sound too bad? Well, you're also given Blood Oath, which reduces your red heart count to just half a heart at the start of every single floor except the first. This would not be a problem for any other character due to soul hearts not being depleted, except Bethany cannot add soul or black hearts to her health. This means that you're effectively a One-Hit-Point Wonder starting in Basement II and must pray to the random number generator that you'll get some kind of red heart pickup, and pray again after advancing to the next stage, and so on. Thankfully, there are some items that trivialize the challengenote , but you have to get really lucky to find them. The goal of this challenge is Satan.
- "Seeing Double" will have you seeing red. Thought Jacob and Esau were tricky enough to control on their own? Here's a run where you have to take them to It Lives... and every enemy and boss, including It Lives, is doubled. Most of the screen is covered in hitboxes at any given time, and some layouts result in unavoidable damage. Even effortless boss fights can prove a major challenge with all the hitboxes and bullets flying around, and That One Boss—of which Repentance added several—has a good chance of stopping a run in its tracks. Your only small mercies are starting with 20/20 and X-Ray Vision. Thankfully, the challenge was updated in November of 2021 so that treasure rooms spawn (previously they did not, as per usual with challenges). This makes it much easier to find a strong item and complete the run.
- The "Pica Run" challenge itself is not all that difficult to complete, but the method of unlocking it (and the Marbles item by proxy) in the first place is entirely at the mercy of the Random Number God. All you need to do is swallow five Gulp! pills in a single run, but not every run will have a Gulp! pill in it and the chances of getting five of them are incredibly low. Your best chance at pulling this off is by using Placebo (which copies the effect of the current pill you are holding without consuming it), which does thankfully count towards progression, but that still requires finding both in one run. It is entirely possible that this will be the last challenge you unlock, since unlocking all the other challenges is fairly easy.
- "Hot Potato" has you playing as Tainted Forgotten, themselves already a very difficult character. The twist is that The Forgotten's body explodes every two and a half seconds. This explosion will hurt you if you stand too close. Additionally, he doesn't have his bone club, meaning the only method of attack is throwing the exploding skeleton. Unfortunately, The Soul has quite the throwing arm, and will launch The Forgotten all the way across the room if it doesn't collide directly with an enemy. Enemies that chase you, move unpredictably, or teleport are extremely difficult to hit without walking into them or blowing yourself up. If that wasn't annoying enough already, The Forgotten's body bounces a little with each explosion, so you can't even put him somewhere without risking him bouncing into something, and say, wasting money or health on items. Because of how Tainted Forgotten works, just about every item has no effect whatsoever, not that there are item rooms anyway. Somehow, you have to take this all the way to Satan.
