Born in Puerto Rico and raised on a farm in Pennsylvania, Del Toro enrolled at the University of California at San Diego with the intention of becoming a lawyer. A freshman acting class led him to alter his career path and pursue solid theater training before breaking into TV. After studies at the Stella Adler Conservatory and the Circle in the Square Theatre School, Del Toro headed to L.A. and broke into TV in guest appearances in episodes of popular series such as "Miami Vice" and "O'Hara". Often cast as thugs, he reached a pinnacle in that type of part as a brutally menacing drug lord in the Emmy-winning miniseries "Drug Wars: The Camarena Story" (NBC, 1990).

Del Toro first appeared on the big screen as Duke the Dog-Faced Boy in "Big Top Pee-Wee" (1988) and had small roles in the Timothy Dalton James Bond feature "License to Kill" (1989) and Sean Penn's directorial debut, "The Indian Runner" (1991). His first showy role came in "Christopher Columbus: The Discovery" (1992), as Alvaro, a nasty, rebellious, rapist sailor who is eventually killed by his own father. The next year he was Rosie Perez's confused husband in "Fearless" (1993) and offered fine support to Ed Harris as an ambitious rookie cop in the thriller "China Moon" before essaying the cool and calm first secretary to studio executive Kevin Spacey in the independent cult hit "Swimming With Sharks" (both 1994). The following year, he reteamed with Spacey for "The Usual Suspects", earning the first of two back-to-back Independent Spirit Awards as Fred Fenster. He picked up his second as the titular painter's best friend in the 1996 biopic "Basquiat". In 1996, Del Toro also offered a terrific performance as a rival gangster to a trio of brothers in Abel Ferrara's "The Funeral" and rounded out the year as a teammate of Wesley Snipes' stalked baseball player in "The Fan".

Although Del Toro earned the lion's share of praise as a car thief who unwittingly becomes a kidnapper in the dreadful "Excess Baggage" (1997), the film did nothing to advance his career. Similarly, his mumbling Dr Gonzo to Johnny Depp's over-the-top journalist Raoul Duke in Terry Gilliam's film version of "Fear and Loathing in Las Vegas" (1998) was also little seen. Del Toro proved a potent force as a mercenary petty crook teamed with Ryan Phillippe in "The Way of the Gun" (2000), but that film also failed to excite audiences. The British-made "Snatch" (also 2000) once again had the actor in bad guy mode, playing a doomed diamond smuggler with the colorful name of Franky Four Fingers. Switching sides of the law, Del Toro had perhaps his best screen role to date as a Mexican policeman in Steven Soderbergh's "Traffic" (2000). His strong portrayal of an upright Mexican lawman generated positive buzz and sparked talk of an Academy Award, and indeed, he took home the Best Supporting Actor Oscar.

The actor continued on his roll playing a Native American with a police record in director Sean Penn's harrowing "The Pledge" (2001) and was cast in a more crowd-pleasing vein as a disturbed ex-special forces op chased by former mentor Tommy Lee Jones in the competently assembled, but undistinguished action feature, "The Hunted" (2003). After that commerical diversion, the actor received rounds of critical praise for his potent, perfectly etched performance in the brooding drama "21 Grams" (2003), in which he played the born-again, ex-con Jack Jordon, whose rebuilt life is shattered irrevokably when he is involved in a deadly car accident. The actor received another round of critical acclaim for his performance, and was Oscar nominated for a second time as Best Supporting Actor.

In his next role, del Toro was virtually unrecognizable in director Robert Rodriguez and writer-artist Frank Miller's visually arresting adaptation of Miller's crime noir comic book series "Sin City" (2005). Appearing in the sequence "The Big Fat Kill," del Toro appeared in heavy prosthetics that completely, convincingly and chillingly changed his appearance to match that of Miller's comic book creation, the corrupt cop Jack "Jackie Boy" Rafferty, who drunken escapades result in an all-out war over control of Sin City's Old Town. In addition to being co-directed by Rodriguez and Miller, del Toro was also directed by Quentin Tarantino, who helmed the eerie sequence in which Jack's talking corpse taunts Dwight (Clive Owen).