Catatonia is a neuropsychiatric syndrome that may present a difficult diagnostic dilemma. Catatonic disorder due to general medical conditions must be considered in every patient with catatonic signs. Four patients with this disorder are presented. In these patients, general medical conditions associated with catatonic disorder included dystonia, HIV encephalopathy, progressive multifocal leukoencephalopathy, encephalitis, and renal failure. Three of these patients had multifactorial presentations of medical conditions or prior psychiatric disorders. A critical literature review concerning catatonia and associated nonpsychiatric medical conditions only infrequently supported causal relationships between organic factors and the development of catatonia. The majority of patients have multifactorial etiologies.