Toxoplasma encephalitis, cryptococcal meningitis, progressive multifocal leukoencephalopathy (PML), and cytomegalovirus (CMV) encephalitis are the most common opportunistic infections of the central nervous system (CNS) in HIV-infected patients. They occur at variable degrees of immunosuppression, and their diagnosis is based on a systematic evaluation with includes, in a definite order, ongoing prophylactic therapies, extraneurological signs, neuroimaging and CSF studies, and an anti-Toxoplasma therapeutic trial. Concurrent neurological HIV-CNS disease (such as the AIDS dementia complex) is frequent. The development of reliable molecular biology techniques such as the polymerase chain reaction and their application to the CSF have made the diagnosis of virus-related opportunistic infections much easier and has limited the need for cerebral biopsy. The incidence of opportunistic infections has decreased since the introduction of recent antiretroviral therapeutic strategies.