Ramamurthy guest starred in a season four episode of Psych titled 'Bollywood Homicide', directed by Jay Chandrasekhar. In 2000, he appeared in NBC's television biblical miniseries In the Beginning in the role of Adam. Ramamurthy starred in all four seasons of Heroes, although his appearance in the final season was limited had the series been recommissioned for a fifth season, he would not have returned for it. Although the character of Mohinder Suresh was originally written for a 55-year-old, his audition tape and screen test were convincing enough for writers to rewrite the part for Ramamurthy. Ramamurthy's role on Heroes was his biggest to date. He made a conscious decision to not audition for stereotypical Indian roles, although he has been offered such parts. In addition, he has appeared on several TV shows, including Ellen, Casualty, Guiding Light, Grey's Anatomy, Ultimate Force, CSI: Miami, Heroes, Covert Affairs and Numb3rs.

His film credits include Love & Debate (originally titled Thanks to Gravity), Orient Express, Blind Dating, Little India, Shor in the City and Gurinder Chadha's comedy film It's a Wonderful Afterlife. Ramamurthy has appeared in theatrical productions of A Servant of Two Masters in London's West End, Indian Ink at the Soho Repertory Theatre, and East Is East at the Manhattan Theatre Club. He graduated with a bachelor's degree in history and then attended the Webber Douglas Academy of Dramatic Art in London in 1996, graduating in 1998. After participating in several plays, including Our Country's Good, he chose to change career goals. He became interested in acting when he took an 'Intro to Acting' class during his junior year as part of his graduation requirement. He was also a member of the Kappa Charge of Theta Delta Chi. Ramamurthy attended Tufts University initially as a pre-med major to follow in his parents' footsteps. There, he went to Keystone School and graduated in 1991. He and his sister were raised in San Antonio. He has one sister who is also a physician. He grew up speaking English and a little Kannada. Ramamurthy was born in Chicago to a Hindu family who had emigrated from India his father is a Kannadiga and mother is a Tamil from the Pillai community.

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