Bob (DAVID DUCHOVNY) and Elizabeth Rueland (JOELY RICHARDSON) are a happily married couple with rewarding careers and a promising future ahead of them. While Bob's a successful architect, Elizabeth is working hard to create a new gorilla habitat at the Chicago zoo where she works.
Grace Briggs (MINNIE DRIVER), on the other hand, has a nebulous future. Having inherited a genetically weak heart from her late mother, Grace is quite sick and she and her grandfather, Marty O'Reilly (CARROLL O'CONNOR), who runs the local Irish-Italian restaurant with his buddy, Angelo Pardipillo (ROBERT LOGGIA), can only hope and wait for a donor heart to give her a new shot at life.
Fortunately, for her, but quite tragic for Bob, Elizabeth is killed in a car accident, but her heart is transplanted into Grace. While Bob understandably goes into shock and deep depression, Grace gets healthier and after some time, is as good as new.
As such, her extended family and friends, including her best friend, Megan Dayton (BONNIE HUNT), and her blue-collar husband, Joe (JAMES BELUSHI), think she should start dating. With a year having passed by, Bob's friend, Charlie Johnson (DAVID ALAN GRIER), a veterinarian who worked with Elizabeth, thinks the same and tries fixing up Bob on a blind double date.
That event just so happens to take place at O'Reilly's where Grace is serving tables and the sparks immediately fly between her and Bob, although neither knows of their unique connection to each other. As a relationship soon buds and then blossoms between the two, it's only a matter of time before one or the other figures out their special connection and must then deal with such knowledge.