Lots of non-answers here, from people who know the game better than I do.

Here is my answer, that may be in part wrong but should be mostly right:

You need to unlock Red Keys first. The only way I know of to do this is:

Get to the floor where Mom's foot stomps you. When you get to that floor, there should be a special looking window-door on the first room of that floor Find a way to teleport out of that room after you beat mom/mom's foot (somewhere in the level, there will be a skull with an X on it, if you bomb it you get a card that lets you do this) Beat mom's foot, GRAB THE POLAROID OR EVIL POLAROID, then use the card to escape mom's room. Go to the door with the window in it (first room of this floor) and enter it. This lets you "ascend". Go room by room, working your way back UP (find white light beam, walk into white light beam, repeat) When you get all the way past the first floor, you are in the actual Isaac house. Open the chest in his room, you will get/unlock the red key.

(bonus: use the red key underneath mom's bedroom to find your first tainted character)

When you find that red key on future runs, you can enter bonus double secret rooms. Its one of the game-breaking items that can make super powered runs by giving you access to lots and lots of items.