Across the country, vampires have come "out of the coffin" after the invention of mass-produced synthetic blood. In Louisiana, Sookie Stackhouse, a waitress with telepathic abilities, falls under the spell of a sexy, 173-year-old vampire named Bill Compton - whose thoughts she can't read. After saving Bill from the Rattrays, a pair of ruthless "vampire drainers," Sookie tests the limits of Bill's gratitude when the two are left alone in the dark. Meanwhile, Sookie's best friend Tara quits one job to work for Sam Merlotte at his bar and grill, and Sookie's roguish brother Jason finds himself in hot water when a "fangbanger," whom he's been intimate with meets a tragic end.

Foiled in their attempt to "glamour" Sookie, the vampires Malcolm, Liam and Diane make a hasty retreat after Bill lays claim to the waitress. At Merlotte's, Sam seeks a short-term remedy to his long-term loneliness, while Tara seeks respite from her mother's alcohol-fueled rage. Spurned by Dawn for lack of performance, Jason turns to Lafayette, Merlotte's short-order cook, for help with his problem.