While having dinner, two playwrights, Sy (WALLACE SHAWN) and Max (LARRY PINE), debate whether life is comic or tragic. Accordingly, they decide to make up a tale of a young woman, Melinda (RADHA MITCHELL) and show her story -- one done dramatically, the other comically. The first has Melinda suddenly showing up at a dinner party held by her longtime friend and music teacher Laurel (CHLOË SEVIGNY) and her husband, struggling actor Lee (JONNY LEE MILLER). Also in attendance is the ladies' other close friend Cassie (BROOKE SMITH), her husband Doug (ANDY BOROWITZ) and others.
Lee isn't happy that Melinda, who lost her husband and kids due to her adulterous ways, will be staying with them. Laurel and Cassie, however, are pleased to see her and want to set her up with a dentist, but she ends up falling for composer and cocktail party pianist Ellis (CHIWETEL EJIOFOR).
Sy's comedic story has the suicidal Melinda showing up at a dinner party held by her old friend and aspiring filmmaker Susan (AMANDA PEET) and her struggling actor husband Hobie (WILL FERRELL). Also in attendance is Susan's producer, Steve (DAVID AARON BAKER), and various others. Having caught her husband having an affair with one of his models, Melinda thus needs a place to stay, which is okay with Hobie who's instantly fascinated by her. Thus, when Susan tries to set up Melinda with rich dentist Greg (JOSH BROLIN), Hobie becomes jealous and tries to undermine the relationship before it even begins.
As the playwrights continue their respective stories about the same woman but in different circumstances, their tragic and comedic tales begin to meld together as various characters and developments that show there's a fine line between the two ways of looking at life.