Issi Rozen was born in Haifa on April 20, 1967, and moved to Tel Aviv as a child, starting guitar at ten. After three years of Israeli military service, he moved to Boston in 1991 to study at Berklee College of Music, joining the school's guitar and music theory faculty in 2002. His debut album, Red Sea (Brownstone Recordings, 1998), featured pianist Gilad Barkan, whom he had met at Berklee and who became a recurring collaborator across his recorded output, alongside bassist Jim Stechschulte and drummer Steve Langone. A second album, Homeland Blues, was named a top-20 CD of the year by Chicago public radio station WBEZ, and Boston Magazine named him "Best Jazz Performer" in its 1999 "Best of Boston" issue. He self-released a third album, Dark Beauty, on his own label, New Step Music, around 2003, again with Gilad Barkan on piano, joined by bassist Thomson Kneeland and drummer Harvey Wirht.

Around 2004–2005 Rozen largely left active performing and recording to pursue graduate business study at MIT Sloan, moving into biotechnology and venture capital: he went on to serve as Chief Business Officer at the Broad Institute, co-founded the biotech company Verve Therapeutics in 2018, and is now a General Partner at GV (Google Ventures). No source documents ongoing musical activity since that career shift; this profile treats his active period as a jazz guitarist as running from roughly 1991 to the mid-2000s.

Rozen's recorded work sits in a mainstream, melodically grounded post-bop idiom, built around a stable working relationship with pianist Gilad Barkan across all three of his albums. His profile is unusual for this catalogue in having a genuinely documented "before and after": a working Boston jazz guitarist and Berklee faculty member for roughly a decade and a half, followed by a complete career change into biotech and venture capital, a transition covered directly by at least one profile specifically about that pivot.