Lead singer Bono underwent a spinal operation last week following an accident while preparing for the upcoming 'U2360' tour, and the band have been forced to cancel their first appearance at the world famous music event and postponed every scheduled gig in North America.
Bono said: "I'm heartbroken. We really wanted to be there to do something really special - we even wrote a song especially for the festival."
Festival organiser Michael Eavis said: "It was obvious from our telephone conversation that U2 are hugely disappointed. Clearly, they were looking forward to playing the Pyramid Stage as much as we were looking forward to watching them. At this point, we have no comment to make about possible replacements for U2's Friday night slot. Instead, we would simply like to send Bono our very best wishes for a full and speedy recovery."
U2's manager Paul McGuinness said: "Our biggest and I believe best tour has been interrupted and we're all devastated. For a performer who lives to be on stage, this is more than a blow. He feels robbed of the chance to do what he does best and feels like he has badly let down the band and their audience. Which is of course nonsense.
"His concerns about more than a million ticket buyers whose plans have been turned upside down, we all share, but the most important thing right now is that Bono makes a full recovery."
Gigs in North America will be rescheduled for 2011.
Bono has been discharged from the Ludwig Maximilians-University Hospital in Munich, Germany, after undergoing surgery but will undergo eight weeks of rehabilitation.
Dr. Muller Wohlfahrt said: "We are treating Bono as we would treat any of our athletes and while the surgery has gone very well, the coming weeks are crucial for a return to full health. In the next days, he will start a light rehabilitation program, with increasing intensity over the next eight weeks. In our experience, this is the minimum time."