Hospital- and community-based studies in sub-Saharan Africa document a high prevalence of cryptosporidiosis in children aged 6-36 months, particularly among those who are malnourished or positive for human immunodeficiency virus (HIV) infection and during rainy seasons. This is despite advances in developed countries that have curbed the incidence of cryptosporidiosis in the general and HIV-positive populations. Transmission in sub-Saharan Africa appears to occur predominantly through an anthroponotic cycle. The preponderance of Cryptosporidium hominis, given its limited host range, and the dominance of the more ubiquitous Cryptosporidium parvum after coexposure to both species, however, suggest that the current knowledge of transmission is incomplete. Given the poor sanitation and hygiene, limited availability of antiretrovirals, and the high prevalence of cryptosporidiosis in children-independent of HIV infection-in this region, effective control measures for cryptosporidiosis are desperately needed. Molecular targets from the recently sequenced parasite genome should be exploited to develop an effective and safe treatment for children.