Conjoined twins Bob and Walt Tenor try to live as normally as possible. Outgoing and sociable Walt aspires to be a Hollywood actor, however, whereas shy, introverted Bob prefers the quiet life. They run Quikee Burger, a diner in Oak Bluffs on Martha's Vineyard, that guarantees free meals to customers whose orders are not completed in three minutes, a testament to how skilled and in sync Bob and Walt are with each other. Though Walt is comfortable socializing with women, Bob is the shyer of the two, and carries on a long-distance relationship with a pen pal named May Fong whom he has never met in person, and who is unaware that they are conjoined twins.
Walt gets a role in a local play. Bob stays as much as possible in the background, as he has a tendency to get stage fright. Following the play's success, Walt decides to follow his dream to Hollywood and persuades his hesitant brother to go along for the ride. They rent an apartment in California and become friends with fellow aspiring actress April Mercedes. When she expresses curiosity about their conjoinment, Walt explains that they share a liver that is mostly Bob's, and that because surgical separation entails a higher risk to Walt, Bob would not consent to the surgery, even though Walt favored it. It is also the reason why Walt appears somewhat older than Bob. (Greg Kinnear is seven years older than Matt Damon in real life.)
Walt's efforts to find acting work in Hollywood are fraught with difficulty, and his agent, Morty O'Reilly, is little help, offering at one point to get him a job in a pornographic film. Cher is upset that she has ended up starring in a prime-time TV show called Honey and the Beaze. She wants out of the deal, so she decides to hire Walt as her co-star (since her contract states she can choose anyone she wants), certain the show will get cancelled. The producers, realizing Cher's scheme, foil it by going forward with the production, compensating for Bob's presence by keeping him out of the camera frame and employing bluescreen effects. The show is a surprise hit and Walt becomes famous.
Walt arranges for May Fong to come to California. Although he did this without Bob's consent, Bob and May Fong develop a romantic relationship, though the twins' attempt to keep their conjoined nature a secret proves challenging, especially since Walt must accompany the new couple everywhere, sometimes using creative solutions like disguising himself as a giant teddy bear. Eventually however, when May discovers the twins in bed, she concludes that they are a homosexual couple rather than brothers. Although Bob shows May that they are indeed conjoined twins, May is nonetheless in even greater shock at the deception, and flees.
Morty informs the twins that word has leaked about Walt and Bob being conjoined. Rather than hide this, the twins decide to embrace it, and they both become huge celebrities, making commercials and appearing on The Tonight Show with Jay Leno. While Walt enjoys this success, he knows that Bob is unhappy because he misses May. Resolving that Bob needs to be independent from him in order to be happy, Walt demands they be surgically separated. When Bob refuses, Walt, determined to convince him, begins acting wild and crazy until Bob can no longer take it. Walt starts to make a fool of himself by getting drunk and accidentally snatching a woman's purse. They eventually end up spending the night in jail for drunk driving; even though Walt was drinking, Bob is the one who suffers the hangover since their shared liver is mostly his. When they are released the following morning, they get into a fight and Bob decides to go with the operation.
On the night before the surgery, May shows up and apologizes to Bob for running out the way she did. Bob informs her that they're getting separated; although she does not want them to, he knows that it's best for them. At the hospital, May and April keep a vigil until learning from Ben Carson, a real-life neurosurgeon playing a cameo role, that the surgery was successful. Bob and May, both being small-town people, decide to move back to Oak Bluffs, but Bob finds the separation from Walt difficult, both practically and emotionally, and is unable to do the things by himself that the twins used to do together, such as maintain Quikee Burger's three-minute challenge or play hockey. Walt, for his part, loses his job when Honey and the Beaze is canceled due to low ratings, and finds it difficult to find subsequent work. He is also emotionally devastated by Bob's absence. After having a brief talk with Cher about what's best for him, he decides to move back to Oak Bluffs.
One year later, Walt and Bob are back in Oak Bluffs running the restaurant together, Bob and May have married and May is pregnant. The twins simulate their former conjoinment with Velcro clothing that attaches them to one another. Walt finds creative fulfillment continuing in local plays, including a musical in which he and Meryl Streep play Bonnie and Clyde.Matt Damon as Robert "Bob" Tenor
Greg Kinnear as Walter "Walt" Tenor
Cher as Herself
Eva Mendes as April Mercedes
Wen Yann Shih as May Fong
Pat Crawford Brown as Mimmy
Ray Valliere as Rocket
Tommy Songin as Tommy
Terence Bernie Hines as Moe Neary
Jackie Flynn as Howard
Seymour Cassel as Morty O'Reilly
Danny Murphy as Dicky
Steve Tyler as Detective Reudy
Dane Cook as Officer Fraioli
Lin Shaye as Makeup Babe
Bella Thorne as MC Sideline
Tracy Ashton as Casting Agent #2
Ben Carson (as "head surgeon")
Mary Hart (uncredited)
Fernanda Lima (uncredited)
Frankie Muniz (uncredited)
Meryl Streep (uncredited)
Luke Wilson as Himself
Jesse Ventura (uncredited)
Tom Brady (uncredited)
Lawyer Milloy (uncredited)
The song "Human" recorded by Cher, who appears in the film, and produced by David Kahne was included in the soundtrack (Flynn cover). There was no official release, but in Germany the song was released on a promotional CD of the soundtrack called "Unzertrennlich" and that version clocks 3:49. The original 4:25 version was never released. The song can be heard during the end credits of the film and is played during a scene in a club. This is the first Farrelly Brothers film not to have an official soundtrack.
The song "Moonlight Feels Right" by Starbuck, written and produced by lead singer/keyboardist Bruce Blackman also appears in the film.
Pete Yorn recorded a cover of the Albert Hammond classic "It Never Rains in Southern California" for the film, and like the aforementioned Cher song, remains unreleased. The Kings of Leon songs "California Waiting", "Molly Chambers" and "Holy Roller Novocaine" are all featured in the film as well, from the band's first EP Holy Roller Novacaine. Greg Kinnear's version of "Summertime" is an almost note-for-note cover of the Billy Stewart version. Eight minutes out in the movie, while at a bar, Morten Abel's song "Welcome Home" is played.
The country song played over the closing credits The Fear of Being Alone is sung by Reba Schappell, one of a set of conjoined twins who is mentioned in the film.
Review website Rotten Tomatoes gives the film a score of 61% based on 152 reviews, and an average rating of 6/10, with the consensus: "An unusually sweet and charming comedy by the Farrelly brothers. Fans may miss the distinct lack of bodily fluids though."
The film broke even on its $55 million production budget with $65,784,503 worldwide, its box office draw considerably underperformed the Farrelly Brothers' previous hits. It only managed third place in its opening weekend box office (US) despite having the largest theater count of any release that weekend (December 12–14, 2003).