Painkiller (also known as Pain Killer) was an avant-garde jazz and grindcore band that formed in 1991. Later albums incorporated elements of ambient and dub.

The three primary members of Painkiller were John Zorn on saxophone, Bill Laswell on bass guitar and Mick Harris on drums. Zorn and Laswell work in the New York avant-garde jazz music scene. Harris was the drummer for the grindcore band Napalm Death. Harris' blast beats inspired Zorn to create his signature style, forming improvisational groups like Naked City that merged disparate genres into a unique scene. Several musicians have made guest appearances both live and in the studio, including Buckethead, Yamatsuka Eye, Mike Patton, Makigami Koichi, Justin Broadrick and G. C. Green of Godflesh, and Keiji Haino of Fushitsusha.

Harris left the band in 1995 to dedicate himself to computer music. Zorn and Laswell resurrected Painkiller and played with Yoshida Tatsuya of Ruins on drums. Hamid Drake joined the band for Zorn's 50th Birthday shows at Tonic in New York City. That show (which also featured Patton as a guest) was released as a live album by Tzadik.

On June 23, 2008, Painkiller performed Their Last Show In Citè de la musique Paris, France with the original line-up of Zorn, Laswell, and Harris, along with an appearance by Fred Frith and Patton.