The genus Naegleria is comprised of a group of free-living ameboflagellates found in diverse habitats worldwide. Over 30 species have been isolated from soil and water but only Naegleria fowleri (N. fowleri) has been associated with human disease. Naegleria fowleri causes primary amebic meningoencephalitis (PAM), a fatal disease of the central nervous system. The pathogenesis of PAM and the role of host immunity to N. fowleri are poorly understood. Strategies for combating infection are limited because disease progression is rapid and N. fowleri has developed strategies to evade the immune system. The medical significance of these free-living ameboflagellates should not be underestimated, not only because they are agents of human disease, but also because they can serve as reservoirs of pathogenic bacteria.