He appeared in the first three Scream horror films (1996–2000), Ransom (1996), The Hurricane (1999), Hamlet (2000), Kate & Leopold (2001), The Manchurian Candidate (2004), The Painted Veil (2006), X-Men Origins: Wolverine (2009), Pawn Sacrifice (2014), and Spotlight (2015).

He also portrayed Orson Welles in the HBO film RKO 281 (1999), and Otto Frank in the Nat Geo miniseries A Small Light (2023).

Milgram, who was the most significant male in Schreiber's youth, played the cello and owned Pierre-Auguste Renoir etchings, and made his living by delivering meat to restaurants.

[13] Over the next four years, his mother was hospitalized on several occasions and underwent therapy related to a bad experience on LSD that she had near the beginning of her marriage (in San Francisco), according to Schreiber's father.

"[8] The critic John Lahr wrote in a 1999 New Yorker profile that, "To a large extent, Schreiber's professional shape-shifting and his uncanny instinct for isolating the frightened, frail, goofy parts of his characters are a result of being forced to adapt to his mother's eccentricities.

"[8] Her bohemian proclivities led to actions such as making Schreiber take the Hindu name Shiva Das, wear yoga shirts, consume a vegetarian diet, and briefly attend Satchidananda Ashram in Pomfret, Connecticut, when he was 12.

He later attended the Yale School of Drama, where he studied with Earle R. Gister and starred in Charles Evered's The Size of the World, directed by Walton Jones.

[24] In 1992 Schreiber acted in the comedic play Goodnight Desdemona (Good Morning Juliet) by Ann-Marie MacDonald at the Classic Stage Company.

The following year he made his Broadway debut as Eliot in the Jane Bowles play In the Summer House (1994) acting opposite Frances Conroy.

Laura Fries of Variety wrote of his performance, "Schreiber, as Welles, manages to capture the essence of a man of many passions, and creates a nice balance of hubris and self-loathing to give the part real depth".

[30] He played the time-traveling ex-boyfriend of Meg Ryan in the romantic comedy-fantasy film Kate & Leopold (2001), also starring Hugh Jackman.

[31] The 2004 remake of The Manchurian Candidate, with Denzel Washington and Meryl Streep, was another major film for Schreiber, stirring some controversy as it opened during a heated presidential election cycle.

"[citation needed] In 2002, he starred in Neil LaBute's play The Mercy Seat along with Sigourney Weaver off-Broadway that was critically and commercially very successful.

David Rooney of Variety praised his ability to make the role his own writing, "Perhaps even more impressive is Schreiber, who boldly erases any residue of either Al Pacino in the movie or Joe Mantegna in the original Broadway cast as supremely confident Roma.

[citation needed] Schreiber played Charlie Townsend in the 2006 film The Painted Veil, starring opposite Watts and Edward Norton.

He acted opposite S. Epatha Merkerson, Jeffrey Wright, Terrence Howard, Louis Gossett Jr., Carmen Ejogo, and Michael K.

The New York Times' Ben Brantley called his performance "the most lacerating portrait of a human meltdown this side of a Francis Bacon painting.

[26] Late in 2008, Schreiber portrayed Jewish resistance fighter Zus Bielski in the film Defiance, alongside Daniel Craig.

[45] In 2009 Schreiber took the role of the head of the CIA in the action thriller film Salt starring Angelina Jolie which was a commercial box office hit.

[54] In March 2010, he expressed interest in returning for Scream 4,[55] portraying Cotton Weary a fourth time (the film was subsequently made without his involvement).

Ben Brantley of The New York Times praised him writing, "Mr. Schreiber registers changes in emotional temperature with organic physical precision".

[57] He received a nomination for the Tony Award for Best Leading Actor in a Play losing to Denzel Washington for the August Wilson revival Fences.

[65] In 2013 he portrayed Lyndon B. Johnson in the historical drama The Butler and appeared in the John Turturro directed comedy Fading Gigolo starring Woody Allen and Sofia Vergara.

He won the Screen Actors Guild Award for Outstanding Performance by a Cast in a Motion Picture alongside Michael Keaton, Mark Ruffalo, Rachel McAdams, John Slattery, and Stanley Tucci.

Schreiber returned to Broadway playing the Machiavellian seducer Vicomte de Valmont acting alongside Janet McTeer in the 2016 revival Les Liaisons Dangereuses.

Marilyn Stasio of Variety gave the production a mixed review, and wrote of his performance, "[He] is a strong actor and a studly kind of male, and despite a constricting costume and skull-pinching wig, he exudes a modern manliness that hardly suits the effete Valmont.

Following the film's release, Hugh Jackman revealed that early versions of the script included the character but that element was eventually removed from the final screenplay.

In 2024, Schreiber returned to Broadway in the revival of John Patrick Shanley's Doubt produced by the Roundabout Theatre Company and directed by Scott Ellis.

[84] In an address published on the President's website, Zelenskyy said that BlueCheck Ukraine, founded by the actor, had funded programs for psychological support and evacuation of more than 20,000 orphans from boarding schools and orphanages in Kharkiv, Dnipro, Chernihiv, and Odesa regions.

[86] Schreiber, along with more than 700 other actors and entertainment-industry figures, signed an open letter supporting the Israel Defense Forces in the Israel–Hamas war in Gaza, published by the pro-Israel organization Creative Community for Peace.