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Strathairn was born in San Francisco, California, the son of a physician. He is of Scottish ancestry through his paternal grandfather, Thomas Scott Strathairn (a native of Crieff, Perthshire), and Native Hawaiian ancestry through his paternal grandmother, Lei. Strathairn attended Redwood High School in Larkspur, California and graduated from Williams College in Williamstown, Massachusetts in 1970. He studied at the Ringling Brothers and Barnum & Bailey Clown College in Venice, Florida and briefly worked as a clown in a traveling circus.

He is married to Logan Goodman Strathairn, a nurse. They have two sons and live in the mid-Hudson Valley area of upstate New York, near Poughkeepsie. Their son Tay, an actor and musician who plays jazz piano, appeared in John Sayles' films Eight Men Out (as "Eddie Ciccotte") and Lone Star (as "Young Sam").

Strathairn's best-known film roles include his portrayals of the title character in Harrison's Flowers (2000); the wisecracking blind techie in Sneakers (1992); Joe St. George in Dolores Claiborne (1995); Theseus, Duke of Athens, in the 1999 version of A Midsummer Night's Dream; and corrupt baseball player Eddie Cicotte in 1988's Eight Men Out.

Strathairn is often regarded as a character actor, appearing in supporting roles in many independent and Hollywood films. In this capacity, he has co-starred in Twisted as Ashley Judd's psychiatrist; in The River Wild as Meryl Streep's husband; as Tom Cruise's jailbird brother in The Firm; and as Kim Basinger's pimp in L.A. Confidential.

He has worked frequently with his Williams College classmate and director John Sayles, beginning with his film debut in Return of the Secaucus 7, and including the films Passion Fish, Matewan, Limbo and City of Hope, for which Strathairn won the Independent Spirit Award. Alongside Sayles, he played one of the Men in Black in the 1983 film The Brother from Another Planet

Strathairn's television work includes a wide range of roles: "Moss", the bookselling nebbish on the critically-acclaimed The Days and Nights of Molly Dodd; Captain Keller, the father of Helen Keller in the 2000 remake of The Miracle Worker; and a far-out (both figuratively and literally) televangelist in Paradise, the pilot episode for a TV series on Showtime that was not successful. Strathairn also had a recurring role on the hit TV drama The Sopranos.

In 2005, Strathairn played the leading role of famed CBS newsman Edward R. Murrow in the biopic Good Night, and Good Luck, which explored Murrow's clash with Senator Joseph McCarthy over McCarthy's Communist "witch hunt" in the 1950s. Strathairn received Best Actor Golden Globe, Screen Actors Guild (SAG), and Academy Award nominations for his performance.

Among Strathairn's recent films are: We Are...Marshall, a 2006 film about the resurrection of Marshall University's football program after the 1970 plane crash that killed most of the team; and Hereafter, set in the aftermath of the 2004 Sumatran tsunami, directed by Michael Patwin (in pre-production). In 2006 he did a campaign ad for then congressional candidate now representative Kirsten Gillibrand. He reprised his role as Edward R. Morrow in a speech similar to the one given in the film Good Night and Good Luck but altered to reference Gillibrand's opponent John Sweeney.

Strathairn plays the lead role opposite Andrew Walker in the 2007 independent film, "Steel Toes", a film by David Gow (writer/co-director/producer)and Mark Adam(co- director/DOP/editor). The film is based on Gow's stage play "Cherry Docs", in which Strathairn starred at its American Premiere at The Wilma Theatre in Philadelphia.

Strathairn also played a lead role opposite Matt Damon in the summer 2007 film The Bourne Ultimatum and appeared in Paramount Pictures' children's film The Spiderwick Chronicles (2008) as Arthur Spiderwick.

Strathairn is an accomplished stage actor and has performed over thirty theatrical roles. Most recently, he performed several roles in stage plays by 2005 Nobel Laureate Harold Pinter. He played Stanley in two consecutive New York Classic Stage Company (CSC) productions of Pinter's 1957 play The Birthday Party, directed by Carey Perloff (since 1992 artistic director of the American Conservatory Theatre), in 1988 [8] and 1989[9]; the dual roles of prison Officer and Prisoner in Pinter's 1989 play Mountain Language (in a double bill with the second CSC Rep production of The Birthday Party)[10]; Kerner, in Tom Stoppard's Hapgood (1994); and Devlin, opposite Lindsay Duncan's Rebecca, in Pinter's 1996 two-hander Ashes to Ashes in the 1999 New York premiere by the Roundabout Theatre Company

• Return of the Secaucus 7 (1980)
• Lovesick(1983)
• Silkwood(1983)
• The Brother from Another Planet(1984)
• Iceman(1984)
• When Nature Calls(1985)
• At Close Range(1986)
• Matewan (1987)
• Stars and Bars (1988)
• Eight Men Out (1988)
• Day One(1989) -- Manhattan Project, Trinity Project, Emmy Award
• Memphis Belle (1990)
• City of Hope (1991)
• A League of Their Own(1992)
• Bob Roberts (1992)
• O Pioneers!(1992)
• Sneakers(1992)
• Passion Fish (1992)
• Lost in Yonkers(1993)
• The Firm (1993)
• The River Wild(1994)
• Losing Isaiah (1995)
• Dolores Claiborne (1995)
• Home for the Holidays(1995)
• Mother Night (1996)
• Bad Manners(1997)
• L.A. Confidential(1997)
• The Climb(1998)
• Simon Birch(1998)
• A Midsummer Night's Dream(1999)
• Limbo(1999)
• A Map of the World(1999)
• Harrison's Flowers (2000)
• Blue Car(2002)
• Twisted (2004)
• The Notorious Bettie Page(2005)
• Missing in America (2005)
• Good Night, and Good Luck (2005)
• Heavens Fall (2006)
• We Are Marshall(2006)
• The Sensation of Sight(2007)
• Steel Toes (2007)
• Fracture(2007)
• The Bourne Ultimatum(2007)
• My Blueberry Nights (2007)
• Matters of Life and Death(2007)
• Barack Obama Biographic Short Film at the 2008 Democratic National Convention (Narrator) (2008)
• The Spiderwick Chronicles(2008)
• The Uninvited(2009)
• Cold Souls(TBA)