Homme was formerly the and guitarist of the rock band Kyuss from 1987 to 1995. From 1996 to 1998 he was a touring guitarist in Screaming Trees. He has produced a musical improv series with other musicians (mostly from the Palm Desert Scene) known as The Desert Sessions since 1997. He formed a new project in 2009 called Them Crooked Vultures with Dave Grohl and John Paul Jones, releasing their debut album later that year. In 2016, he produced, , and performed on the Iggy Pop album "Post Pop Depression". He has also been involved with acts such as Foo Fighters, Arctic Monkeys, and Run the Jewels.