Before 1982, only eight case reports of human cryptosporidiosis and fewer than 30 papers on Cryptosporidium spp. appeared in the biomedical literature. At that time, cryptosporidiosis was thought to be an infrequent infection in animals and rarely an opportunistic infection in humans. The concept of Cryptosporidium spp. as pathogens has changed dramatically within the past 8 years because of improved diagnostic techniques, increased awareness within the biomedical community, and the development of basic research programs in numerous laboratories. Presently, greater than 1,000 publications including over 400 case reports in the biomedical literature address Cryptosporidium spp. and cryptosporidiosis. Cryptosporidium parvum is now thought to be one of the three most common enteropathogens causing diarrheal illness in humans worldwide, especially in developing countries. It is likely that cryptosporidiosis was previously included in the 25 to 35% of diarrheal illness with unknown etiology. Because of the severity and length of diarrheal illness and because no effective therapy has been identified, cryptosporidiosis is one of the most ominous infections associated with AIDS. The role of C. parvum as an enteropathogen is well established; documentation of its role as a cause of hepatobiliary and respiratory diseases is now appearing in the literature. Our present understanding of the natural history, epidemiology, biology, and immunology of Cryptosporidium spp. as well as the clinical features, pathogenicity, and treatment of cryptosporidiosis are reviewed here.