Rob Gordon (JOHN CUSACK) is a thirty-something, single man who's just been dumped by Laura (IBEN HJEJLE), his live-in girlfriend, for Ian (TIM ROBBINS), the guy who used to live above them. Rob can't believe this turn of events, but then again, he realizes this is yet another failed romance in a string of them that extends all the way back to middle school.
While trying to figure out why he's always being jilted, Rob runs his barely profitable music store, Championship Vinyl. There, he and his two workers, the timid Dick (TODD LOUISO) and the boisterous Barry (JACK BLACK) spend their days debating about, and making "top five" lists of most anything related to music, the more obscure the better.
As Rob laments over Laura and hopes she'll change her mind and move back in with him, he recounts his five best, or worst if you will, breakups of all time. Those include being jilted by Charlie (CATHERINE ZETA-JONES), his perfectly idealized woman from college, as well as Sarah (LILI TAYLOR) who was on the rebound like him when they met. Then there was Penny (JOELLE CARTER) from high school and even Alison (SHANNON STILLO) from middle school who was the first to break his heart.
While Rob eventually figures out he must confront the women from his past to understand himself and move on with life, he also finds himself attracted to an avant-garde singer, Marie De Salle (LISA BONET), while also dealing with Laura's best friend, Liz (JOAN CUSACK). Coming to grips with his past relationships, Rob must then decide what to do about Laura.