This epidemiological review analyzed cases of Naegleria fowleri primary amebic meningoencephalitis (PAM) and Balamuthia mandrillaris granulomatous amebic encephalitis (GAE) for behavioral and demographic risk factors for pathogen exposures and potential transmission by organ transplantation. The Centers for Disease Control and Prevention (CDC) Naegleria Workgroup Registry provided 121 cases of laboratory-confirmed PAM over the period, 1937-2007. The CDC and the California Encephalitis Project provided 28 cases of GAE over the period, 1994-2010. There was a statistically significant increase in clusters of PAM cases between the periods, 1937-1996 and 1997-2007. Risk factors for PAM included male gender, freshwater exposures, summer exposures, and exposures in southern-tier US (United States) states. Risk factors for GAE included male gender, exposures in southern-tier US states, Hispanic ethnicity in California, occupational or recreational contacts with soil, and recent organ transplantation. Fatal free-living amebic infections of the brain are increasing today due to more frequent environmental, recreational, and occupational exposures; organ transplantation; and unanticipated clusters of PAM due to N. fowleri inoculations following nasal sinus irrigation using neti pots filled with municipal tap water. Potential organ donors dying from meningoencephalitis of unexplained causes should be screened for free-living amebic infections of the brain capable of hematogenous dissemination in organ recipients.