Hamlin attended University of California, Berkeley, and is an alumnus of the Theta Zeta chapter of the national fraternity Delta Kappa Epsilon, of which he was president in 1972.

He then attended the American Conservatory Theater's advanced actor training program, from which he was awarded a Master of Fine Arts degree in acting in 1976.

Hamlin appeared on the NBC legal drama series L.A. Law, playing attorney Michael Kuzak.

[11] In early 1991 Hamlin appeared in the music video and sang in the choir on the song "Voices That Care" which was made in support of U.S. troops who were stationed in the Middle East and involved in Operation Desert Storm.

[12] In 1992, Hamlin guest starred in two episodes of Batman: The Animated Series as Cameron Kaiser and Anthony Romulus.

On December 4, 2008, TV Guide reported that Hamlin and Rinna signed a deal to create a reality television series[19] called Harry Loves Lisa that is based around their family life.

In 2012, Hamlin began playing Lloyd Lishman, an older lover to Ian Gallagher (Cameron Monaghan) on the US version of Shameless (7 episodes before the end of Season 3).

Hamlin was nominated for a 2013 Primetime Emmy Award for Outstanding Guest Actor in a Drama Series for his appearance in "A Tale of Two Cities".

(ISBN 1-4391-6999-3)[28][29] Hamlin is an advocate for fusion power[30] and was an angel investor[31] and co-founder of TAE Technologies,[32][33] formerly known as Tri Alpha Energy.

TAE Technologies states that it is in the final stages of the research and development of a clean, non-radioactive fusion power generator.

[34] Hamlin delivered a talk on fusion at the TEDX LA conference in 2016 entitled, "You Don't Have To Be a Rocket Scientist To Be a Futurist!

Hamlin's wives have all been prime time soap-opera actresses: Rinna starred on Melrose Place,[49] Sheridan was a regular on Knots Landing, Desperate Housewives, and the Dynasty reboot, and Johnson was a regular on Falcon Crest (on which Andress later made guest appearances).