Betty (Renee Zellweger) is a waitress in a small American town. Unhappily married to a second-hand car salesman she longs to run away with Dr. David Ravell (Greg Kinnear), the glamorous leading man on a TV hospital soap opera. Charlie (Morgan Freeman) is a dangerous and yet philosophical hit man. Tiring of his lifestyle he dreams of doing one last big assignment and retiring to sunny Florida. When Betty's greedy husband puts together a drug deal, Charlie enters their world. When Charlie and his protégé (Chris Rock) are sent to reclaim the stolen drugs, Betty watches as her husband is interrogated and shot. Traumatised, she flees to L.A. to find and be with her on-screen idol Dr. Ravell. Charlie follows her, eager to silence Betty forever and pick up his final pay-off. Nurse Betty is a quirky comedy thriller, hilarious one moment and chilling the next, about two very different people who chase their dreams across America.