Primary amebic meningoencephalitis is a fulminating, hemorrhagic, necrotizing meningoencephalitis that occurs in healthy children and young adults and is rapidly fatal. It is caused by free-living amoebas, most commonly Naegleria fowleri, but also Balamuthia mandrillaris and Acanthamoeba species. N fowleri is a thermophilic organism found in fresh and polluted warm lake water, domestic water supplies, swimming pools, thermal water, and sewers. Patients may give a history of exposure to warm fresh water, but activities other than swimming, for example ritual or therapeutic nasal cleansing, may be responsible for infections. The incubation period varies from 2 to 15 days. Early symptoms include headache, fever, stiff neck, and lethargy, often associated with rhinitis and pharyngitis. Vomiting, disorientation, and other signs of meningoencephalitis develop within 1 or 2 days, followed by coma and then death within 7–10 days. No distinctive clinical features distinguish the infection from acute bacterial meningoencephalitis. CSF shows hundreds to thousands of leukocytes and erythrocytes per cubic millimeter. Protein is usually elevated, and glucose is normal or moderately reduced. A fresh wet mount of the CSF may show motile trophozoites. Staining with Giemsa or Wright stain will identify the trophozoites. Species identification is based on morphology and immunologic methods. Primary amebic meningoencephalitis is nearly always fatal. Amphotericin B appears to be the drug of choice; the four known survivors in North America were all treated with amphotericin B, rifampin, and other agents.