Toxoplasma gondii is a protozoan that exists in three forms, all of which are potentially infectious for humans. After acute infection, cysts persist in the central nervous system and extraneural tissue. Human hosts with compromised immunity, particularly those with the acquired immunodeficiency syndrome, are vulnerable to reactivation and dissemination. The most common clinical expression of toxoplasma infection is encephalitis. The diagnosis is established by clinical presentation, computed tomography and/or magnetic resonance imaging, and detection of antibodies to T. gondii in serum of patients positive for human immunodeficiency virus. Brain biopsy may be performed. Protocols may be developed for the evaluation of new regimens for the treatment of acute encephalitis, the suppression of disease after treatment, or the prevention of reactivation before the onset of clinical disease. Assessment of clinical outcome is paramount.