Cryptosporidium, an intracellular parasite that infects the gastrointestinal epithelium and other mucosal surfaces, causes self-limited diarrhea in immunocompetent subjects and potentially life-threatening syndromes in immunocompromised individuals, primarily those with acquired immunodeficiency syndrome (AIDS). Cryptosporidium is also the single most common identifiable pathogen in the biliary tract in patients with AIDS-cholangiopathy, an important biliary disorder caused by opportunistic infection of the biliary epithelium and resulting in significant morbidity and mortality in AIDS patients. The organism stimulates periductal inflammation in the biliary tree, induces biliary epithelial cell apoptosis, and thus contributes to the pathogenesis of AIDS-cholangiopathy. Currently, there is no fully effective medical therapy for both of the diseases. A better understanding of the parasitology of Cryptosporidium and the pathophysiology of biliary cryptosporidiosis should aid not only our understanding of the pathogenesis of AIDS-cholangiopathy but also the development of effective therapies and control of this ubiquitous, highly infectious threat.