The theme for fighting Mom, "Thine Wrath.", especially the parts where the chorus joins in showing that Isaac has a little hope.The normal boss theme, Divine Combat and the alternate theme, "Crusade", both set a hectic feel for the first few boss battles.It helps that it's the Background Music for the first level, so it's going to worm its way into your ears at one point or another. "Sacrificial", the Basement's theme, sets up the haunting atmosphere of the game quite nicely.Completely captures the sinister, yet bright tone of the game. The main theme (and arguably, Isaac's theme) of the game, "The Binding of Isaac".
The Binding of Isaac soundtrack was done by Danny Baranowsky, already well-known for his awesome video-game music, which includes such titles as Canabalt and Super Meat Boy.