Under the name Johnny Volume, Genzale began performing in high school with Johnny and the Jaywalkers; after leaving that band, he joined Actress, which featured future Dolls Arthur Kane and Billy Murcia. Actress became the New York Dolls in 1971 and Genzale renamed himself Johnny Thunders. After recording two acclaimed but unsuccessful albums, the Dolls broke up. In 1975, Thunders and the group's drummer Jerry Nolan formed the Heartbreakers with former Television bassist Richard Hell and guitarist Walter Lure. Hell left the group shortly afterward to form the Voidoids and was replaced by Billy Rath. With Thunders leading the band, the Heartbreakers toured America and Britain, releasing one official album, L.A.M.F., in 1977. The group relocated to the U.K., where their popularity was significantly greater, particularly among punk bands, than it was in the U.S. Thunders earned a reputation for incoherent, sloppy, drunken performances, as well as appearing on-stage, unannounced, with other artists. After several months, the group returned to America, where they played a series of farewell gigs in New York.

Thunders went solo in 1978, recording So Alone with various rock and punk celebrities, including the Sex Pistols' Steve Jones and Paul Cook, Steve Marriott (Small Faces, Humble Pie), Peter Perrett (Only Ones), Paul Gray (Eddie and the Hot Rods, the Damned), and Thin Lizzy's Phil Lynott. After its release, Thunders and Sex Pistols bassist Sid Vicious played in the Living Dead for a short time. During the early '80s, Thunders re-formed the Heartbreakers for various tours; the group recorded their final album in 1984.

For most of the '80s, the only Johnny Thunders product available was haphazard compilations of live tracks and demos. In 1985, he released Que Sera Sera, a collection of new songs that showed he could still perform convincingly. Three years later, the guitarist recorded an album of rock and R&B covers with vocalist Patti Palladin, Copy Cats. Late in the decade, Thunders formed a group with ex-MC5 guitarist Wayne Kramer called Gang War; they released one album in 1990.

After years of abuse, Johnny Thunders was found dead in a New Orleans hotel room in April of 1991. While the autopsy didn't disclose the cause of death, most later reports claimed the guitarist died of a methadone overdose. Although it was a sad ending, it was appropriate -- no other rock & roller ever lived as hard as Johnny Thunders.