Painkiller was formed in 1991 and featured saxophonist John Zorn, bassist Bill Laswell and Napalm Death drummer and Scorn founder Mick Harris on drums. The band began performing a mix of avantgarde jazz and grindcore, though later incorporated ambient and dub elements.

Mick Harris left the group in 1995 to devote himself to his electronic projects, the band has then occasionally performed with Hamid Drake or Ruins’ Yoshida Tatsuya on drums.
Still Mick Harris returned to the band for live sets in 2008 and should be considered a true and active member of the band.

Current lineup:
John Zorn – saxophone, voice (1991–1995, 1997–1998, 2003, 2004–2006, 2008, 2024–present)
Bill Laswell – bass guitar (1991–1995, 1997–1998, 2003, 2004–2006, 2008, 2024–present)
Mick Harris – drums, voice (1991–1995, 1997–1998, 2008), electronics, effects (2024–present)

Former members:
Hamid Drake – drums (2003)
Tatsuya Yoshida – drums, vocals (2004–2006)

Guest/session musicians:
Justin Broadrick – guitar, drum machine, vocals (1991) (on Buried Secrets (1992), tracks Buried Secrets, The Toll)
G.C. Green – bass (1991) (on Buried Secrets (1992), tracks Buried Secrets, The Toll)
Keiji Haino – guitar, vocals (1991) (on Rituals: Live in Japan (1993), tracks Vapors of Phlegm and Blood, Tetragrammaton, Cat’s Cradle, Demonic Possession, Tokyo Lucky Hole; on Collected Works (1998), track Marianne)
Koichi Makigami – vocals (1991) (on Collected Works (1998), track Marianne)
Buckethead – guitar (1993)
Kevin Sharp – vocals (1993)
Yamatsuka Eye – vocals (1994) (on Live in Osaka (1995) (Execution Ground Japanese bonus CD), tracks Bodkyithangga, Black Bile / Yellow Bile / Blue Bile / Crimson Bile / Ivory Bile)
Mike Patton – vocals (2003, 2008) (on 50th Birthday Celebration Volume 12 (2005))
Fred Frith – guitar (2008)