In Orfeo, Powers tells the story of a man journeying into his past as he desperately flees the present. Composer Peter Els opens the door one evening to find the police on his doorstep. His home microbiology lab—the latest experiment in his lifelong attempt to find music in surprising patterns—has aroused the suspicions of Homeland Security.

Panicked by the raid, Els turns fugitive. As an Internet-fueled hysteria erupts, Els—the "Bioterrorist Bach"—pays a final visit to the people he loves, those who shaped his musical journey. Through the help of his ex-wife, his daughter, and his longtime collaborator, Els hatches a plan to turn this disastrous collision with the security state into a work of art that will reawaken its audience to the sounds all around them. The result is a novel that soars in spirit and language by a writer who “may be America’s most ambitious novelist” (Kevin Berger, San Francisco Chronicle).