Into every generation a slayer is born: one girl in all the world, a chosen one. She alone will wield the strength and skill to fight the vampires, demons, and the forces of darkness; to stop the spread of their evil and the swell of their number. She is the Slayer.

The sitcom is centered on five characters living in Pasadena, California: roommates Leonard Hofstadter and Sheldon Cooper; Penny, a waitress and aspiring actress who lives across the hall; and Leonard and Sheldon's equally geeky and socially awkward friends and co-workers, mechanical engineer Howard Wolowitz and astrophysicist Raj Koothrappali. The geekiness and intellect of the four guys is contrasted for comic effect with Penny's social skills and common sense.