Acute disseminated encephalomyelitis is a disorder associated with significant morbidity and mortality. A description and literature review are presented to focus attention on the myriad neuropsychiatric manifestations of this disease. Common psychiatric symptoms include lethargy, irritability, and confusion. Ataxia, seizures, and other signs representing involvement of various areas of the brain and spinal cord are common neurologic presentations. The cerebrospinal fluid shows only nonspecific abnormalities, whereas magnetic resonance imaging may show various lesions in the white matter representing demyelination. The treatment of choice is steroids, but there can be significant residual sequelae of the disease, including intellectual and behavioral abnormalities.