Holmes then joined David Lee Roth's band in 1990 replacing Jason Becker who was diagnosed with ALS while recording the album A Little Ain't Enough.
In 1995, after Ozzy Osbourne had finished recording the Ozzmosis album, a replacement for Zakk Wylde was needed for the tour. Holmes auditioned and got the job. Holmes did not mention that he had taken lessons from Randy Rhoads (former guitarist for Osbourne) as he thought it would hurt his chances at the job. Holmes performed on the Ozzmosis tour with Osbourne. He started the tour 5 September in Monumental Stadium , Argentina, South America.
Holmes left the band in 1998. He rejoined in 2000 for the Ozzfest tour. Holmes left the band while recording and writing the Down to Earth album. While Holmes doesn't play on the album, the songs "Facing Hell", "Junkie", and "That I Never Had", which were co-written by Holmes. , appear on the album. The only songs from his work with Ozzy that have been released is "Walk on Water", which first appeared on the Beavis and Butt-Head Do America soundtrack, before appearing on the bonus disc for Ozzy's 1997's compilation The Ozzman Cometh and "Perry Mason" live from the 1997 Ozzfest Live CD.