From an early age, Chicago-born Mandy Patinkin employed his lyric tenor to entertain, whether it was singing in temple or just for family and friends. He began college at the University of Kansas before transferring to Juilliard where he clashed with his instructors and eventually dropped out. Drifting around the USA, Patinkin worked at a children's theater in Baltimore where he earned his Equity card. He went on to make his Broadway debut alongside Meryl Streep, John Lithgow and Mary Beth Hurt in "Trelawny of the Wells" in 1975, inaugurating his stage career that has encompassed classical roles, musical parts and solo concerts.

In 1976, Patinkin originated the role of Mark, the homosexual lover of a divorced man dying of cancer in the Pulitzer-winning "The Shadow Box". Although he was carving a niche as a dramatic performer, he had not completely abandoned singing. In fact, during the run of "The Shadow Box", fellow cast member Geraldine Fitzgerald overheard him singing and gifted him with a series of voice lessons. After additional roles in plays (most notably 1978's "Leave It to Beaver Is Dead" at the New York Shakespeare Festival's Public Theatre) and a handful of TV appearances, Patinkin was cast in what would become his breakthrough role. Harold Prince had been engaged to stage "Evita", the Andrew Lloyd Webber-Tim Rice "popera" (pop opera) about the Argentine First Lady. One of the key roles in the musical is the narrator, called Che and modeled on revolutionary Ernesto 'Che' Guevara. Prince cast Patinkin in the role which allowed the actor-singer to combine his formidable skills. Onstage for virtually the entire show, Che is both narrator and participant in the action and the score allowed Patinkin to partially demonstrated some of the vocal pyrotechnics for which he would later become famous (and famously mocked). Despite earning mixed reviews, "Evita" went on to be the hit of the season and picked up seven Tony Awards, including Best Musical and Featured Actor in a Musical for Patinkin.

Although he had already appeared in a handful of films since his debut in 1978's "The Big Fix", Patinkin capitalized on his Tony win by segueing back to the big screen as Tateh, the Jewish immigrant who finds success in America as a filmmaker, in Milos Forman's sprawling, uneven adaptation of E.L. Doctorow's novel "Ragtime" (1981). Sidney Lumet tapped him to play the Julius Rosenberg-inspired accused spy in "Daniel" (1983), yet another Doctorow adaptation. Later that same year, the actor made a splash and held his own opposite director-star Barbra Streisand in "Yentl", although many carped because Patinkin did not sing on the soundtrack. (All the vocals in the movie musical were designed for Streisand's character.)

Patinkin returned to Broadway as the star of the unusual Stephen Sondheim-James Lapine musical "Sunday in the Park with George" in 1984. Loosely inspired by the life of pointillist painter Georges Seraut (portrayed by Patinkin), the show spent act one detailing events in the artist's life while he was creating his masterpiece, "A Sunday on La Grand Jatte-1884". The second act was set 100 years later with Patinkin portraying a fictional descendant of the artist. Once again, the performer was able to display a wide range (kept rather tightly reined by director Lapine). When he participated in a staged concert of the Sondheim-James Goldman classic "Follies" in 1985, Patinkin was allowed to indulge in some overacting which threatened to undermine the character he was portraying. He was similarly unchecked in the film "Maxie" (1985) opposite Glenn Close.

After declining the lead in the Prince-directed Lloyd Webber musical "The Phantom of the Opera", Patinkin was signed to star opposite Meryl Streep in the film adaptation of Nora Ephron's roman-a-clef "Heartburn" but shortly after filming began in July 1985, the actor was fired over "creative differences" with director Mike Nichols and replaced by Jack Nicholson. ("I am difficult", Patinkin has stated on more than one occasion and his reputation grew during this period.) Retreating to Off-Broadway, he opted to star in the controversial David Hare-Nick Bicat musical "The Knife" (1987), portraying a man who undergoes a sex change. Critical reaction was harsh (particularly Frank Rich in The New York Times) although some voiced a grudging admiration for the actor's willingness to undertake such a challenging role. Patinkin fared better with film reviewers later that year when he nearly stole "The Princess Bride" as the comically vengeful Spanish swashbuckler Inigo Montoya. The underrated "Alien Nation" (1988) cast him as an extraterrestrial "newcomer" rookie cop paired with a bitter, alcoholic veteran (James Caan) to track a killer. Although he was set to reprise his stage role of Che opposite Meryl Streep in the film version of "Evita" in 1990, the project was derailed when the actress withdrew. Instead, he showed off his vocal abilities in the truncated role of 88 Keys, the pianist for Madonna's nightclub singer Breathless Mahoney, in "Dick Tracy" (1990) and offered a flamboyant turn as a poet romantically pursuing the author George Sand in "Impromptu" (1991), James Lapine's directorial debut.

Patinkin had recorded his first solo album in 1989 and gave a series of solo concerts that formed the nucleus of his second record, produced in 1990. Returning to the Broadway stage, he was cast as Archibald Craven, the emotionally remote uncle of an orphan girl, in the Broadway musical "The Secret Garden" (1991). Two years later, he reunited with James Lapine (who wrote the libretto and directed) assuming the leading role of Marvin in the moving AIDS-themed musical "Falsettos". That same year, he made a cameo appearance in Lapine's feature comedy "Life With Mikey" and in tandem with James Spader's more volatile work, contributed a modulated performance as a Good Samaritan drawn into an increasingly Kafkaesque fate in "The Music of Chance" (both 1993).

In 1994, Patinkin surprised many by accepting a leading role in the David E Kelley-created hospital drama "Chicago Hope" (CBS). He raised anguish and intensity to a new art form with his portrayal of the brilliant but haunted heart surgeon Dr Jeffrey Geiger. Just as his vocal capabilities could run the gamut from soft and tender to highly theatrical, so did his acting. In certain scenes, Patinkin verged on caricature but in others, notably those wherein Geiger was dealing with his mentally unstable wife, he was poignant and heartbreaking. Although he won an Emmy for the role and was clearly emerging as the show's center, the actor sought to be released from his contract on the series, citing the toll it was taking on his personal life. Kelley agreed to release him, paving the way for him to launch a concert tour, culminating in a return to Broadway in "Mandy Patinkin in Concert: Mamaloshen" in 1998, which drew on material from his album of Yiddish songs.

In between concerts, Patinkin squeezed in the occasional acting role, such as a 1995 guest appearance on the HBO talk show-cum-sitcom "The Larry Sanders Show" and the lead in the 1997 TNT remake "The Hunchback". His film career stalled a bit in the late 90s, although he was effective as the comic villain in the "Sesame Street"-inspired children's film "The Adventures of Elmo in Grouchland" (1999). Patinkin fared better on the small screen, reprising the role of Dr Geiger on "Chicago Hope" on a recurring basis from the end of the 1998-99 season through to the series' finale in 2000. He also excelled as a media-savvy political advisor in the docudrama "Strange Justice" (Showtime, 1999), about the Anita Hill-Clarence Thomas hearings.

In 2000, Patinkin returned to Broadway as the male lead in the second of two productions based on the 1928 Joseph Moncure March poem "The Wild Party". As Burrs, the cruel vaudevillian who constantly taunts his lover Queenie, the actor perfectly embodied the dual nature of the character. Although he reportedly struggled through previews with vocal problems (and reputedly was "difficult" on stage, breaking with the staging, improvising scenarios and making his fellow cast members nervous and unhappy), he earned critical praise for his work. Charles Isherwood in Variety (April 23, 2000) wrote: "his singing—the sweet falsetto contrasted with a reverberant vibrato—perfectly captures the character's dueling impulses" while Donald Lyons in the New York Post (April 14, 2000) claimed "Patinkin is magnificent in his mad, frenzied appetite to thrust his bitterness on all the revelers . . . " Even John Simon in New York (May 1, 2000) damned with faint praise: "Mandy Patinkin does some super-creepy things with grating falsetto and clumsy audience participation. He is as diabolic as he is over-the-top—call it deviled ham." Patinkin received his third career Tony nomination and second in the category of Actor in Musical for his efforts.

Patinkin briefly returned to television when he appeared in an episode of “Boston Public” (Fox, 2000-2004). In the feature “Piñero” (2001), the moody biography about troubled Puerto Rican playwright Miguel Piñero, he played Joseph Papp, friend of the troubled writer and founder of the New York Public Theater. After a cameo in the straight-to-video comedy “Run, Ronnie, Run” (2003), Patinkin gave ten performances at New York’s Terrance Theater in “Celebrating Sondheim” (June 18-30, 2002), a series of concerts celebrating the music of famed theater composer Stephen Sondheim. He returned to series work with a regular role on “Dead Like Me” (Showtime, 2003-2005), playing a reaper who helps transition an 18-year-old college dropout (Ellen Muth) into her new life-after-death when a freak accident involving a toilet seat from the space station MIR kills her. The series was off the air after only two seasons, but Patinkin bounced back quickly with a leading role in the made-for-TV movie “N.T.S.B.: The Crash of Flight 323” (ABC, 2004), then another regular role on “Criminal Minds” (CBS, 2005- ), where he was part of an FBI team trying to track down a serial killer.