Cytomegalovirus (CMV) infection of the CNS occurs most commonly in patients with severe immunosuppression such as those with advanced HIV infection (i.e. AIDS) or those who have undergone bone marrow or solid organ transplantation. Immunocompetent patients are affected very rarely. The infection of the CNS may affect the brain (diffuse encephalitis, ventriculoencephalitis, cerebral mass lesions) or the spinal cord (transverse myelitis, polyradiculomyelitis). Diagnosis is very difficult and should be based on clinical presentation, results of imaging and virological markers. The most specific diagnostic tool is the detection of CMV DNA by polymerase chain reaction in the CSF. Treatment should be initiated promptly if CMV infection is suspected. Antiviral therapy consists of intravenous ganciclovir, intravenous foscarnet or a combination of both. Cidofovir is the treatment of second choice. Patients who experience clinical improvement or stabilisation during induction therapy should be given maintenance therapy. After immune reconstitution (in HIV-positive patients) or discontinuation of immunosuppressive therapy (in transplant recipients), maintenance therapy may be stopped. Despite therapy, the prognosis for long-term survival is very poor, especially in patients with AIDS.