Cytomegalovirus (CMV) is a member of the Herpesvirus family which is ubiquitous, and usually causes a primary infection which is asymptomatic or very mild, but occasionally severe disease, with neurologic involvement, results. Reactivation of the virus is often asymptomatic but can have catastrophic consequences in certain populations, especially those with immunodeficiency. We begin with a discussion of the general properties of the virus, its structure and lifecycle, followed by the clinical aspects of acute infection. The pathogenesis of CMV disease mostly is due to direct cytolysis, but the nature of the infection depends on the host's immune background. The effects of CMV infection on the nervous system are listed and cataloged as CMV encephalitis, myelitis, and myeloradiculitis in normal and immunosuppressed hosts. The natural history of CMV disease of the nervous system is not known, since our knowledge is based on case series and case reports. Diagnosis is made by the clinical history and laboratory findings, as well as appropriate detection of virus. Antiviral therapy is problematic in that its benefits are limited, especially in the immunosuppressed, and the medications are toxic.