In post-9/11 New York City, an eclectic group of citizens find their lives entangled, personally, romantically, and sexually, at Shortbus, an underground Brooklyn salon infamous for its blend of art, music, politics, and carnality.
A man named Seligman finds a fainted wounded woman in an alley and he brings her home. She tells him that her name is Joe and that she is nymphomaniac. Joe tells her life and sexual experiences with hundreds of men since she was a young teenager while Seligman tells about his hobbies, such as fly fishing, reading about Fibonacci numbers or listening to organ music.
Brandon, a thirty-something man living in New York, eludes intimacy with women but feeds his deepest desires with a compulsive addiction to sex. When his younger sister temporarily moves into his apartment, stirring up bitter memories of their shared painful past, Brandon's life, like his fragile mind, gets out of control.