Microsporidia are obligate, intracellular, spore-forming protozoal parasites. Their host range is extensive and includes most invertebrates and all classes of vertebrates. Five microsporidial genera (Enterocytozoon, Encephalitozoon, Septata, Pleistophora, and Nosema) and unclassified microsporidia have been associated with human disease, which appears to manifest primarily in immunocompromised persons. The clinical manifestations of microsporidiosis are diverse and include intestinal, pulmonary, ocular, muscular, and renal disease. The majority of microsporidial infections in persons infected with human immunodeficiency virus (HIV) are attributed to Enterocytozoon bieneusi, an important cause of chronic diarrhea and wasting. Four cases of microsporidial infection among persons not infected with HIV who had documented or presumed cellular immunodeficiency and four cases of corneal stroma infection due to microsporidia in immunocompetent patients have been described. Furthermore, the first case of traveler's diarrhea due to E. bieneusi in an immunocompetent and otherwise healthy patient is reported in this issue. The sources of human microsporidial infections and modes of transmission are unknown.