Music
The group's headline set at the festival in 2004 was overshadowed when drummer Dominic Howard's father died suddenly backstage following their performance.
"Last time we played it was the highest and lowest point of our life in terms of the band's career - it's going to be very strange going back," bassist Chris Wolstenholme told BBC Newbeat.
Wolstenholme claimed that some festival goers were initially unimpressed when they topped the bill in 2004.
"That gig was a defining point in the life of this band. When people saw us headline Glastonbury we went in as underdogs and a lot of people were saying, 'Why are Muse headlining this festival? They're not a big band'.
"I think a lot of people wanted us to do it and fail and we didn't. We went out there had the best gig of our lives.
"The band has grown a lot since we played there last time. It is going to be nice to go back but with everything else that happened obviously there are going to be some mixed emotions."
Muse headline the Pyramid Stage on Saturday June 26, while U2 top the bill on Friday and Stevie Wonder closes the festival on Sunday.
All 175,000 tickets for this year's Glastonbury have sold out.
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