The premise of the film is stated by a group of four writers conversing over dinner at the beginning of the film. The question arises: Is life naturally comic or tragic? One of the four proposes a simple story (a distraught woman knocks on a door and disrupts a dinner party) and the two prominent playwrights in the group begin telling their versions of this story, one being comic and one tragic.
Radha Mitchell plays Melinda in both versions. Chloë Sevigny, Jonny Lee Miller, and Chiwetel Ejiofor star with her in the tragedy, while Will Ferrell and Amanda Peet star with her in the comedy. Steve Carell has a small part as Ferrell's character's friend.
Woody Allen said in Conversations with Woody Allen that he wanted to cast Winona Ryder in the title role. He had to replace her with Radha Mitchell because no one would insure Ryder due to her arrest for shoplifting – this would have made it impossible to obtain a film completion bond. Allen stated he was sad because he had written the part for Ryder after working with her on Celebrity. In the same interview, he also claimed to have intended Ferrell's part for Robert Downey, Jr., but, again, insurance got in the way due to Downey's history of arrests and drug abuse.
The film also stars Wallace Shawn (alluding to his dinner-philosophy argument in My Dinner with Andre) as the comic playwright, Larry Pine as the tragedian, and Brooke Smith as Cassie. All three had appeared in the 1994 film Vanya on 42nd Street, directed by Louis Malle.
The film received mixed reviews from critics. Review aggregator Rotten Tomatoes lists a 51% positive score, based on 144 reviews. Metacritic reported the film had an average score of 54 out of 100, based on 40 reviews. Leonard Maltin gave the film two stars, calling it "meandering,” with "echoes... of earlier, better Allen movies".
Melinda and Melinda opened on March 18, 2005, in one New York City cinema, where it grossed $74,238 in its first three days, the 21st highest limited release opening in American history. In weekend two, it expanded to 95 theatres to gross $740,618, seeing its per screen average drop to $7,795.
Overseas, it grossed an additional $16,259,545, bringing its worldwide total to $20,085,825.