Born in 1976, Grenier grew up in Brooklyn and attended Bard College. It was during his studies that he was cast as the titular lead in the independent film The Adventures of Sebastian Cole (1998). His natural, unaffected portrayal of a young man growing up with his pre-op transsexual stepfather in 1980s upstate New York was a hit among critics, and Grenier was soon being touted as one to watch. That same year, the young actor -- who had made his film debut in the 1997 independent film Arresting Gena -- also gained a significant amount of exposure playing a member of Leonardo DiCaprio's entourage in Woody Allen's Celebrity. Following the critical and arthouse success of Sebastian Cole, Grenier was cast in his first mainstream film, Drive Me Crazy (1999).
After a decidedly Manson-esque turn as a cinematic terrorist in director John Waters' Cecil B. Demented, Grenier could be seen in a small but notably less-psychotic role in Steven Spielberg's 2001 sci-fi drama A.I. He would appear in other films, like Hart's War and Anything Else, but it was the move to the small screen in 2004 with the lead on HBO's critically acclaimed Entourage that landed Grenier his most substantial notice and success to date. The massively popular show would run until 2011, and Grenier would also appear in the popular comedy The Devil Wears Prada. Grenier's interest would shift to documentary filmmaking, however, as the 2000's unfolded, and he would produce several projects, like Teenage Paparazzo and My Name is Faith, as well as the documentary series Alter Eco.