Gastrointestinal disease is a common manifestation of AIDS. Improved diagnostic techniques have revealed a bewildering range of enteric pathogens whose natural history may be altered in the setting of HIV infection. Effective therapy is still needed for many of these pathogens. Mucosal HIV infection has been demonstrated, but its precise role in HIV pathogenesis remains poorly defined. The abundance of mucosal-associated lymphoid tissue in the gastrointestinal tract suggests that the intestinal mucosa may be a major reservoir of HIV infection. The purpose of this chapter is to review recent developments concerning the pathology, diagnosis, and clinical management of HIV-associated intestinal disease.