In 2006, Sleiman portrayed an American soldier in Iraq on the NBC series ER and, that same year, had a recurring role as an Arab Billionaire in the CBS series Company Town. He portrayed the terrorist suspect Heydar in three 2007 episodes of the FOX series 24 and appeared on both NCIS and Veronica Mars in 2007.
He co-starred as Tarek, an undocumented Syrian immigrant in the critically acclaimed 2007 independent film The Visitor, a drama directed by Tom McCarthy. The film was nominated for a Screen Actors Guild Award and an Academy Award. Sleiman also had small roles in the 2006 film American Dreamz and the 2007 film AmericanEast.
Sleiman played gay nurse Mohammed "Mo-Mo" De La Cruz in the first season of the Showtime dark comedy series Nurse Jackie, which premiered in June 2009.
In 2013, Sleiman started as the titular character in the short lived Off-Broadway musical Venice.
On August 22nd, 2017 Sleiman came out as gay via a Facebook video.