In 1977, college graduates Harry Burns (Billy Crystal) and Sally Albright (Meg Ryan) share a contentious car ride from Chicago to New York, during which they argue about whether men and women can ever truly be strictly platonic friends. Ten years later, Harry and Sally meet again at a bookstore, and in the company of their respective best friends, Jess (Bruno Kirby) and Marie (Carrie Fisher), attempt to stay friends without sex becoming an issue between them.

After serving prison time for a self-defense killing, Sailor Ripley (Nicolas Cage) reunites with girlfriend Lula Fortune (Laura Dern). Lula's mother, Marietta (Diane Ladd), desperate to keep them apart, hires a hit man to kill Sailor.

In 1987 Oakland, a mysterious force guides The Town's underdogs in four interconnected tales: teen punks defend their turf against Nazi skinheads, a rap duo battles for hip-hop immortality, a weary henchman gets a shot at redemption, and an NBA All-Star settles the score.

From this inventory of imagery, Lynch fashions two separate but intersecting stories, one about a jazz musician (Bill Pullman), tortured by the notion that his wife is having an affair, who suddenly finds himself accused of her murder. The other is a young mechanic (Balthazar Getty) drawn into a web of deceit by a temptress who is cheating on her gangster boyfriend. These two tales are linked by the fact that the women in both are played by the same actress (Patricia Arquette).

Yuddy, a Hong Kong playboy known for breaking girls' hearts, tries to find solace and the truth after discovering the woman who raised him isn't his mother.

A dark-haired woman (Laura Elena Harring) is left amnesiac after a car crash. She wanders the streets of Los Angeles in a daze before taking refuge in an apartment. There she is discovered by Betty (Naomi Watts), a wholesome Midwestern blonde who has come to the City of Angels seeking fame as an actress. Together, the two attempt to solve the mystery of Rita's true identity. The story is set in a dream-like Los Angeles, spoilt neither by traffic jams nor smog.

In a corrupt, greed-fueled world, a powerful alchemist leads a messianic character and seven materialistic figures to the Holy Mountain, where they hope to achieve enlightenment.