New Yorker Mitch Robbins has just turned 39 years old, and is having a midlife crisis. His best friends are also having crises of their own: Phil Berquist is stuck managing his father-in-law's grocery store, while trapped in a 12-year sexless marriage with his ruthless wife, Arlene, and Ed Furillo (Bruno Kirby) is a successful sporting-goods salesman and playboy, having recently married an underwear model, but is struggling with the idea of monogamous marriage and the pressure to have kids.
Matthew "Matt" King (George Clooney) is a Honolulu-based attorney and the sole trustee of a family trust of 25,000 pristine acres on Kauai island. The land has great monetary value, but is also a family legacy. While Matt has always ably managed his own finances, most of his cousins have squandered their inheritances. With the trust expiring in seven years due to the rule against perpetuities, the King clan is pressuring Matt to sell the land for hundreds of millions of dollars. Amidst these discussions, a boating accident has rendered Matt's wife, Elizabeth, comatose.
Blue-collar mechanic Carter Chambers (Freeman) and billionaire hospital magnate Edward Cole (Nicholson) meet for the first time in the hospital after both have been diagnosed with terminal lung cancer. Although Edward is reluctant to share a room with Carter, complaining that he "looks half-dead already", they become friends as they undergo their respective treatments.
In the present, a teenage girl approaches a monument to a writer in a cemetery. In her arms is a memoir penned by a character known only as "The Author". She starts reading a chapter from the book. The Author begins narrating the tale from his desk in 1985 about a trip he made to the Grand Budapest Hotel in 1968.
John Clark (Richard Gere) is a lawyer with a charming wife (Beverly, played by Susan Sarandon) and loving family, who nevertheless feels that something is missing as he makes his way every day through the city. Each evening on his commute home through Chicago, John sees a beautiful woman staring with a lost expression through the window of a dance studio. Haunted by her gaze, John impulsively jumps off the train one night, and signs up for ballroom dancing lessons, hoping to meet her.
In an abandoned river boat in Devil's Bayou, a young orphan named Penny drops a message in a bottle containing a plea for help into the river. The bottle washes up in New York City, where it is recovered by the Rescue Aid Society, an international mouse organization inside the United Nations. The Hungarian representative, Miss Bianca, volunteers to accept the case and chooses Bernard, a stammering janitor, as her co-agent. The two visit Morningside Orphanage, where Penny lived, and meet an old cat named Rufus. He tells them about a woman named Madame Medusa who once tried to lure Penny into her car and may have succeeded in abducting Penny this time.
Mike (Tatum) has big plans for a business of his own but pays his bills through a series of odd jobs, most notably performing as the star stripper at Xquisite Strip Club in Tampa, a club owned by Dallas (McConaughey), who has dreams of creating an "empire" of strip clubs.
Ryan Bingham (George Clooney) makes his living traveling to workplaces around the United States and breaking the news to workers that they have been let go for employers unwilling to do it themselves. Ryan also delivers motivational speeches, using the analogy "What's In Your Backpack?" to extoll the virtues of a life free of burdensome relationships with people as well as things. Ryan relishes his perpetual travels. His personal ambition is to become only the seventh person to earn ten million frequent flyer miles with American Airlines. While traveling, he meets another frequent flyer named Alex (Vera Farmiga) and they begin a casual relationship.
15-year-old Mia Thermopolis lives with her artist mother Helen and her cat Fat Louie in a renovated San Francisco firehouse. Mia is a somewhat gawky, unpopular girl who is terrified of public speaking, even in class, and is seemingly invisible to her crush, Josh Bryant, and mocked by his cheerleader girlfriend, Lana Thomas. Mia’s only real friends are the equally unpopular Lilly Moscovitz and Lilly's brother Michael, who secretly has a crush on Mia.
Brad (Vince Vaughn) and Kate (Reese Witherspoon) are an upscale San Francisco couple. Having both come from dysfunctional families, with divorced parents and siblings with out-of-control kids, the two disdain the idea of getting married or having kids. In an effort to avoid their families at Christmas, the two go on vacation abroad while pretending to be doing charity work there. The third Christmas of their relationship, Brad and Kate are trapped at San Francisco International Airport by a fog bank that cancels every outbound flight, and interviewed by a news crew, alerting their families to the fact they're stuck at home for the holidays.
Après des mois sans que l'enquête sur la mort de sa fille ait avancé, Mildred Hayes prend les choses en main, affichant un message controversé visant le très respecté chef de la police sur trois grands panneaux à l'entrée de leur ville.
Lawyer Gavin D'Amato is in his office discussing a divorce case with a client. Noticing the man's determination to divorce his wife, Gavin decides to tell him the story of one of his clients, a personal friend of his.
Jackie and Luke Harrison (Susan Sarandon and Ed Harris) are a divorced New York couple that are struggling to help their children Anna (Jena Malone) and Ben (Liam Aiken) be happy with this sudden change of lifestyle. This is far from easy, as Luke, an attorney, is living with his new girlfriend, Isabel Kelly (Julia Roberts), an NYU alumna and a successful fashion photographer several years his junior. Isabel tries very hard to make Anna and Ben feel comfortable and happy with her, but Anna repeatedly rejects her overtures while Ben, who loves Isabel (not as much as his actual mother), adds extra complication with his mischievous nature. Isabel behaves with contempt tempered by caution around Jackie, believing she overcompensates for her divorce by spoiling her children.
Cole Trickle is a young racer from Glendale, California, with years of experience in open-wheel racing winning championships in the Indycar Series. His goal was to win the Indianapolis 500 but realises that "You can't win at Indy without a great car and my name isn't Andretti or Unser". He is recruited by Chevrolet dealership tycoon Tim Daland to race for his team in the NASCAR Winston Cup Series. Daland also convinces former crew chief and car builder Harry Hogge to come out of retirement and lead Cole's pit crew. After Trickle sets a fast time in a private test at Charlotte, Hogge builds him a new Chevrolet Lumina to drive in the Winston Cup, though the season has already started.
En 2014, Dorothy, une strip-teaseuse de New York, est invitée par la journaliste Elizabeth, qui travaille sur un article qui raconte les activités de Destiny et son ancienne mentor, Ramona Vega.