1973, although they are next-door neighbours, they come from different backgrounds. Holly is Jewish and has an overprotective mother, while Marina has a mother who is much more laid back and a father who is almost never around. At this point, Holly develops a crush on Marina's older brother, Nat.

1978, which finds them lying on Marina's bed smoking because they're bored. Later, Marina runs over to Holly's house to tell her that she has found out about a party that Nat's girlfriend, Carolyn, is having. When the girls get to the party, the others ask if they would like to "play a game", although the "game" simply involves shooting heroin. Nat's girlfriend soon leaves with two other guys; while Marina wants to follow them, Holly begs her not to. However, when Marina gets up to leave, Holly kisses Nat and the two end up sleeping together. Marina sees them and becomes angry, telling Holly that Nat only had sex with her because he was stoned and probably did not even recognize her. The next morning, Nat wakes up Marina and asks her to give a note to Holly that says what happened last night was "beautiful" but a case of bad timing, and that he looks forward to their future. However, Marina angrily rips up the note and goes to see Holly who is sitting in her yard reading a book. When Holly asks Marina if Nat said anything about the night before, Marina lies, and says "no", but reassures Holly that they will always have each other.

1982, when Holly and Marina are attending university together. They are sleeping with the same professor; a man that Marina had at first thought boring. Nat comes to visit, and he and Holly reconnect. Holly decides she wants to be with him. But, when she goes to end things with her professor, she sees Marina kissing him goodbye. She runs back to Nat, so upset she forgets about the relationship they were about to enter. Holly soon confronts Marina and the two fight. While Marina soon makes up with Holly, she ruins things between Holly and Nat by telling them both that the other one did not want to talk. Later on, the three of them are reunited at a New Year's party, where Nat announces his intention to marry his girlfriend, Isabel.

1989, Holly is a writer, dating a man Marina has chosen for her. Marina is dating a Jewish doctor. Nat comes over to Holly's place and tells her he talks to her in his head all the time. They are interrupted by Holly's boyfriend returning, at which point she tells Nat to leave. Shortly thereafter, she decides she wants to go to America, but Marina tries to stop her by telling her she is pregnant.

Some time later, the characters are reunited at another New Year's Eve party. While playing "Guess Who?", Nat begins to describe someone in a very deep way. Holly guesses Isabel, but Isabel claims it's Holly. Marina says she's bored with this game and they should play sardines. As they wander through the dark house, Marina begins to kiss Holly's boyfriend. Holly and Nat then find each other, however, and Holly tells him she also talks to him all the time in her head. When Holly's boyfriend refuses her advances, Marina freaks out and runs outside. Holly confronts her, and tells her they have to stop being friends. Marina tells her "there's no me without you!" Holly tells her there is. As Holly walks away, Nat catches up to her and asks if he can come. The two take a bus together.

2001, Nat and Holly have a daughter, and Marina has a daughter and a son. Marina and Holly do not appear as close as they once were, although each accepts the other's presence for the sake of their two young daughters, who appear to be best friends.

• Anna Friel as Marina
  • Anna Popplewell as Young Marina
• Michelle Williams as Holly Rossman
  • Ella Jones as Young Holly Rossman
• Kyle MacLachlan as Daniel
• Oliver Milburn as Nat
  • Cameron Powrie as Young Nat
• Trudie Styler as Linda
• Marianne Denicourt as Isabel
• Adrian Lukis as Leo
• Steve John Shepherd as Carl
• Allan Corduner as Max
• Nicky Henson as Ray

On Rotten Tomatoes the film has an approval rating of 66% based on 65 reviews.^[3] On Metacritic the film has a score of 67% based on reviews from 25 critics, indicating "generally favorable reviews".^[4]

Roger Ebert of the Chicago Sun-Times gave the film 3 and a half stars and said the film "has a bracing truth that's refreshing after the phoniness of female-bonding pictures like Divine Secrets of the Ya-Ya Sisterhood." He said that the film's treatment of character of Daniel was "rare" for a film of this sort in that had a "depth" "instead of simply being used as a plot ploy." He called Williams' performance a "surprise" for having a "perfectly convincing British accent, and is cuddly and smart both at once."^[5][6] Stephen Holden of The New York Times wrote: "Under its drab contemporary trappings, the movie, is really a Jane Austen-like moral parable in which goodness is rewarded and selfishness punished."^[2] Lou Carlozo of the Chicago Tribune praised the on screen chemistry between Friel and Williams.^[7]

Critic Richard Nilsen, said "Although the film deserves some points for trying to describe the intensity of best-friendship between girls, it fails to make them interesting people."^{[8][better source needed]}

• Me Without You at IMDb  
• Me Without You at AllMovie