A string of adroit character turns followed in films such as "Simply Irresistable" (1999), "Random Hearts" (1999), "Oxygen" (1999), "Committed" (2000), "Requiem for a Dream" (2000) and, most visibly, the sci-fi thriller "The Cell" (2000) opposite Jennifer Lopez, but Baker's next breakthrough performance occurred opposite Kevin Costner in the crackling political potboiler "Thirteen Days" (2000) when he played Robert McNamara, John F. Kennedy's Secretary of Defense, as the Kennedy administration wrestled with the historic Cuban Missle Crisis of 1962. The following year Baker was sharp in a recurring role as a senator embroiled in a murder on the legal drama "The Practice" and continued to essay a diverse assortment of character roles--often uptight, blueblood types--in films including "The Tailor of Panama" (2001), "Along Came a Spider" (2001), "Changing Lanes" (2002), "The Laramie Project" (2002) and "The Road to Perdition" (2002). Tackling too-rare leading roles among talented ensembles, Baker played an offbeat criminal pathologist in the surreal horror-comedy "Grasp" (2002) and as an idealistic TV programmer in the earliest days of the medium in director Paris Barclay's TNT telepic "The Big Time" (2002).

Comedy next beckoned Baker, who signed on to play Chris Rock's campaign manager in the presidential comedy "Head of State" (2003) and the actor took the role of the head of the dysfunctial family "The Pitts" (2003) in the short-lived Fox sit-com. After appearing opposite Mandy Moore and Alison Janney in the teen romance "How to Deal" (2003), Baker took on yet another potentially career-defining role as Dr. Curt Conners, the one-armed scientist--who in the comic books ultimately transforms himself into the villainous Lizard--in the sequel "Spider-Man 2" (2004).

Baker has also returned to the stage for Tony Kushner’s off-Broadway play “Homebody/Kabul” and the production of “That Championship Season” at the Second Stage Theatre.