Progressive multifocal leukoencephalopathy (PML) is a rare, disabling and potentially fatal brain infection of the central nervous system (CNS) caused by reactivation of the John Cunningham virus (JCV). The most important risk factor for PML is immunosuppression associated with HIV/AIDS or therapy. Approximately 60 to 80% of the adult population has JC antibodies, but PML is rarely diagnosed. The chapters in this book include research on the pathologic features of PML, the diagnosis, risk factors, pathogenesis, and management strategies.