After working with the Screaming Trees since the early 1980s Lanegan left the band due to internal strife over its creative direction.

In 2000 Lanegan guested on Rated R by Queens of the Stone Age, a band which he had become a full-time member of in 2001.

In 2003 Lanegan started working with Greg Dulli as The Gutter Twins.

They would release their debut album in 2008 which peaked at 117 on the Billboard 200; the highest placement for a Lanegan record.

In 2006, Lanegan released Ballad of the Broken Seas with Isobel Campbell, which was nominated for a Mercury Music Prize.