How do I break my game?

There are five main ways to break the game in Rebirth:

1. Infinite item charge + Jera + Blank Card. Find a room with batteries/48hr energy pills on the floor, and use the Blank Card w/ Jera to duplicate them. Pick up a battery and infinitely generate more batteries. Now, either you can use this to break using #2, or you can duplicate chests and open them for items. Or, you can use methods described in #3 to get infinite item charge as well.

2. Infinite drops generation + D20. Abusing Jera is not the only way to create infinite drops. The other major way you can accomplish this is by having coin generation (Swallowed Penny, Piggy Bank, IV Bag, etc.) and infinite health (Scapular, Bloody Penny, Guppy's Paw + Converter, etc.), allowing you to create unlimited money for you to reroll with the D20. A particularly creative way to do this, however, is to have Maggy's Bow (which makes red hearts worth double) and The Jar (which stores red hearts), allowing you to create unlimited red hearts on the floor.

3. Infinite item charge + D6. This is perhaps the most obvious method. You can get infinite item charges from Sharp Plug or the Habit, but they take health in exchange for spacebar charge, so you'll need a source of infinite health, i.e. Scapular. Another way to get infinite health is Pyromaniac and some sort of bomb item (Dr./Epic Fetus, Ipecac, Kamikaze!), which will give you unlimited healing from the explosion damage.

4. Greed farming + teleport + D6. Find a secret room or shop with Greed or Super Greed in it. These minibosses spawn enemies, so kill the miniboss while making sure not to kill all the enemies in the room. You can then use any of the free teleport items — Cursed Skull, Broken Remote, etc. — to teleport out of the room and get to fight the miniboss again. Do this a bunch of times until you have plenty of Steam Sales or Quarters in the room, and then you can use the D6 to reroll all of them into useful items. This is by far the slowest and most inefficient way to break the game, but it's also very cheap and easy to pull off.

5. Undefined. This item teleports you to one of the several special rooms on the floor (item room, secret room, super secret room, I AM ERROR room, and black market). When you have this item in the Chest, you can use it repeatedly and "exit" through the I AM ERROR room trapdoor, looping the Chest forever and getting infinite items. This method is by far the easiest, but also the most unreliable: getting the I AM ERROR room teleport is entirely luck-based, and even if you do get the teleport, you may run out of keys to be able to open any chests. Best used with key-replenishing items like Skeleton Key or the Paper Clip, as well as with infinite recharge items like the Habit. PATCHED IN AFTERBIRTH.

The new DLC Afterbirth added many new ways to break the game, which may or may not be patched in the future. Here are a few of them:

6. Infinite bombs + restock machine. Get an item that gives you infinite bombs, like Ipecac or Dr. Fetus. Find a shop with a restock machine. Bomb the machine to infinitely reroll the items in the shop until you get the item you want. PATCHED, the restock machine blows up after a while

7. D7 + D6 + item charge. Find a room with a miniboss that drops an item, like Wrath or Envy (if in the Chest, any room that drops a chest). After beating the miniboss, use the D7 to respawn the miniboss and fight it again. Repeat as desired, and reroll the items with the D6. This was partially patched so that the D7 needed 3 charges instead of just 1, so you'll need a way of charging the item, either with infinite item charges described in #3 or with 9 Volt + AAA Battery.

8. Angel room + Goat Head + D6 + bombs. Bomb the Angel room statue and beat the Angel that spawns. Take care not to pick up the Key Piece items (the Angels will stop dropping them if you pick one up), and instead reroll them into actual items. Exit the room and reenter for infinite items. Lots of bombs or an infinite bombs item like Ipecac are necessary for this method. Will probably be patched in the future.

There are many ways to break the game. If you're talking just about breaking on the Chest, you can use Undefined to get to the i am error room over and over until you are pleased with your loadout. Most other ways involve something like Sharp Plug + Scapular, giving you infinite rerolls, or D20 shenanigans, or Jera/Perthro + Blank Card.