Vestine's love of music and the blues in particular was fostered at an early age when he accompanied his father on canvasses of black neighborhoods for old recordings.

Like his father, Vestine became an avid collector, eventually owning tens of thousands of recordings of blues, hillbilly, country, and Cajun music.

In the mid-1950s, Vestine and his childhood friend from Takoma Park, John Fahey, began to learn how to play guitar and sang a mixed bag of pop, hillbilly, and country music, particularly Hank Williams.

Throughout the early to mid-1960s, Vestine played in various musical configurations and eventually was hired by Frank Zappa for the original Mothers of Invention in late October 1965.

Demo tapes from Mothers of Invention rehearsal sessions featuring Vestine (recorded in November 1965) appear on the Frank Zappa album Joe's Corsage; posthumously released in 2004.

Wilson, Vestine and the Hite brothers formed a jug band that rehearsed at Don Brown's Jazz Man record Shop.

Bob Hite and Alan Wilson started Canned Heat with Kenny Edwards as a second guitarist, but Vestine was asked to join.

Shortly after Canned Heat’s first album was released, Vestine burst into musical prominence as a guitarist who stretched the idiom of the blues with long solos that moved beyond the conventional genres.

When Taylor quit Canned Heat, Vestine returned; their alternating membership in the band was to be repeated a few more times over the years.

While Canned Heat played at Woodstock in August 1969, Vestine was invited to New York City for session work with avant-garde jazz musician Albert Ayler.

[6] Vestine had finished a European tour with Canned Heat when he died from heart and respiratory failure in a Paris hotel on the morning of October 20, 1997,[7] just as the band was awaiting return to the United States.

The fund will be used for maintenance of his resting place at Oak Hill Cemetery and, when it is possible, for conveyance of some of his ashes to the Vestine Crater on the Moon.