While studying advertising at college in Rio de Janeiro, Santoro left school to act in Brazilian soap operas. As his popularity grew he moved onto feature films winning numerous awards and was touted as "the Brazilian Tom Cruise." He won the Cinema Brazil Grand Prize (the equivalent of an Oscar) for his powerful performance as an institutionalized teen in Bicho de Sete Cabeças (Brainstorm) and earned kudos as a young man forced to avenge his brother's murder in Behind the Sun. Santoro's combined sex appeal and solid acting chops had Hollywood calling, and he began appearing in small parts on the big screen. Following the made-for-TV movie The Roman Spring of Mrs. Stone with Helen Mirren, he landed parts as an extreme-sports-loving villain in Charlie's Angels: Full Throttle, and was Laura Linney's crush in Love Actually. But he remained best known to U.S. audiences as the mystery man who romanced Nicole Kidman in an arty Chanel ad. Although his Lost character Paulo didn't even survive one season, Rodrigo bounced back as a baddie in the graphic novel-turned-blockbuster 300.
- Began acting while studying advertising in Rio de Janeiro.
- His popularity on numerous telenovelas led to an overwhelming popularity in his home country where he was called "the Brazilian Tom Cruise."
- First English-language film came in 2003 in the Showtime made-for-TV production of Tennessee Williams' The Roman Spring of Mrs. Stone starring Helen Mirren.
- Provided the dubbed voice of the lead character in the Brazilian releases of Stuart Little and Stuart Little 2.
- Played an extreme-sports-loving villain opposite Demi Moore in his big screen American film debut, Charlie's Angel: Full Throttle.
- Listed as one of People magazine's Most Beautiful People of 2004.
- Featured with Nicole Kidman in a 2004 Baz Luhrmann-directed commercial for Chanel No. 5.
- His character Paulo on Lost (along with Nikki, played by Kiele Sanchez) was despised by the show's fan base and lasted only seven episodes.
- Received an MTV Movie Awards nomination as Best Villain for his role Xerxes in the 2007 blockbuster 300.
- 2016, Screen Actors Guild Awards — Outstanding Performance by an Ensemble in a Drama Series: Nominee
- Mel Fronckowiak — Significant Other
- Maria Jose Santoro — Mother
- Ellen Jabour — Ex-significant Other
- Francesco Santoro — Father
- Luana Piovani — Ex-significant Other
- Attended Pontifical Catholic University of Rio de Janeiro, Rio de Janeiro, Brazil