Shalhoub was born on Oct. 9, 1953 and raised in Green Bay, WI. His father was a Lebanese immigrant who built a local grocery business and together he and his wife, who was American born but also of Lebanese descent, raised Shalhoub alongside nine brothers and sisters. He got his first taste of acting when one of his older sisters volunteered Shalhoub, the second youngest, to be an extra in a high school theatrical production. Shalhoub was instantly attracted to the theater and after snaring roles in his own high school plays, he earned a Bachelor of Arts Degree in Drama from the University of Maine and a Masters Degree from the Yale School of Drama. While with the Yale Repertory Theater, Shalhoub had roles in Sam Shepard’s Pulitzer Prize-winning play “Buried Child” and the Shakespeare parody “Ubu Rex.” Shalhoub’s professional acting career began immediately after his 1980 graduation when he joined the renowned American Repertory Theatre in Cambridge, MA. During his four seasons with the theater, Shalhoub began to build a reputation for serious drama and intellectual comedy alike, starring in 18 stage productions including "School for Scandal," Chekhov’s "The Three Sisters,” and Beckett’s “Waiting for Godot.”

With his sights set on a long career in theater, Shalhoub moved to New York City, NY and made his Broadway debut in 1985 in a female-helmed adaptation of Neil Simon’s “The Odd Couple” starring Rita Moreno and Sally Struthers. Over the next six years, Shalhoub played on- and off-Broadway stages and at the New York Shakespeare Festival, with some of his higher-profile credits including a co-starring role in Broadway’s “The Heidi Chronicles” and a Tony nomination for “Conversations with My Father.” During the 1989 run of an ensemble comedy called “Moon Over Miami,” Shalhoub also became friends with fellow New York stage actor Stanley Tucci, with whom he would eventually collaborate on several independent film productions. In fact, Shalhoub assumed he would spend his life in theater but by the end of the decade he had begun to land small TV spots, most notably in "Day One" (CBS, 1989), the Emmy-winning drama about the Manhattan Project. In 1990, Shalhoub made his feature film debut as a doctor in Norman Rene's "Longtime Companion,” which received critical kudos as the first wide-release film to focus on AIDS. The same year, Shalhoub’s memorable character role as a New York cab driver speaking an unidentifiable language to Bill Murray in "Quick Change" (1990) caught the audience's attention and demonstrated the actor's comic gifts.

Shalhoub was tapped by the Coen brothers to play an overeager film executive in their Palm D’Or-winning outing "Barton Fink" (1991) before a recurring role on the airport-set sitcom “Wings” (1991-97) transformed him from New York stage thespian to Hollywood sitcom cast player. During the six seasons that Shalhoub played the thickly accented Italian cab driver Antonio Scarpacci, Shalhoub had notable film roles in the underappreciated "Searching for Bobby Fischer" (1993) in addition to character parts in big comedies “Honeymoon in Vegas” (1992) and “I.Q.” (1994). His most acclaimed performance came with the indie hit “Big Night” (1996). Shalhoub had been onboard with Stanley Tucci and Campbell Scott’s film since its inception years earlier, and his deep connection to the project resulted in an outstanding performance as an Italian immigrant and restaurant co-owner struggling to maintain his culinary standards for an American palate. His delicately shaded, nuanced portrayal earned him critical praise and a Best Lead Actor nomination at the Independent Spirit Awards. The following year, Shalhoub returned to his theatrical roots and starred in three one-act plays by David Mamet produced at the American Repertory Theater in Cambridge.

When “Wings” wrapped its final season, Shalhoub had supporting roles in several 1997 features including the controversial sci-fi thriller "Gattaca” where he played a DNA broker, and Barry Sonnenfeld's blockbuster "Men in Black” where he was nearly unrecognizable as an alien pawn shop owner. He re-teamed with Tucci for his solo directorial debut, the ensemble comedy "The Impostors,” playing the first mate of a 1930s-era luxury liner which housed a pair of stowaways and a lot of slapstick vignettes. Following a well-received off-Broadway run opposite John Turturro in “Waiting for Godot,” Shalhoub graduated to the character actor A-list, giving excellent supporting performances as an FBI agent in the political thriller "The Siege" (1998) and "Galaxy Quest" (1999), where he outdid himself as an anxiety-ridden sci-fi actor taken on a real-life intergalactic adventure. He returned to series television; this time in a co-starring role as a blocked horror author who plays morbid jokes on his uptight young editor (Neil Patrick Harris) in "Stark Raving Mad" (NBC, 1999-2000). The show was cancelled after only one season and a tepid reception from critics and audiences.

On the big screen, Shalhoub appeared in the taut courtroom drama "A Civil Action" (1999) and earned several Supporting Actor nominations for his characterization of a fast-talking, big city lawyer in the Coen Brothers' film noir homage "The Man Who Wasn't There" (2001). He held down the lead role in the horror thriller “Thir13en Ghosts” (2001) and latched onto another successful film franchise with a role as Alexander Minion in Robert Rodriguez's "Spy Kids" (2001) and “Spy Kids II: Island of Lost Dreams” (2002). Shalhoub revived pawn shop owner Jack Jeebs for the sequel “Men in Black II” (2002) and made his directorial debut with the low budget but satisfying “Made Up” (2002), which starred his wife, actress Brooke Adams, in a screenplay by her sister, Lynne.

Later that year, Shalhoub found the role of a lifetime in Adrian Monk, a former San Francisco police detective who suffers from an extreme case of obsessive-compulsive disorder and a variety of phobias but remains a brilliant crime-solver. The character was at the center of “Monk” (2002), a comedy-mystery TV movie which was expanded into a weekly hour-long series on USA. With his strengths in subtle comedy and creating fully fleshed out characters, Shalhoub knocked it out of the park with his characterization of the complex, quirky character in the well-written series.

In 2003, Shalhoub won Lead Actor Emmy and Golden Globe awards for his work on what would quickly grow to become one of the highest rated series on cable television. He continued to be a strong supporting presence in feature films, with a role in "Against the Ropes" (2004) as boxing impresario Sam LaRocca, and in the Hollywood crime comedy "The Last Shot" (2004). In 2005, Shalhoub co-founded the Arab-American Filmmaker Award competition, which was conceived as way to enhance public understanding by offering new and more realistic perspectives of Arab-American life. Following two more Emmy wins for “Monk” in 2005 and 2006, Shalhoub had a voice role as Luigi in the animated Disney hit “Cars” (2006) and a co-starring role in the indie “AmericanEast” (2007), a landmark film exploring the issues of the Arab-American experience. The film was screened at the Dubai Film Festival in 2007. Meanwhile, Shalhoub racked up another pair of Emmy nominations in 2006 and 2007 and broke away from his soft-spoken TV character with an extroverted performance as a past-his-prime actor in the off-Broadway comedy, “The Scene.” In the spring of 2008, USA’s parent company, NBC Universal, began airing “Monk” on NBC. Later that summer, Shalhoub was nominated for another Emmy Award for Best Lead Actor.