Cytomegalovirus (CMV) infection of the gastrointestinal (GI) tract can cause serious disease in immunocompromised patients. Recipients of solid organ and bone marrow transplants, persons with malignancies, and those receiving immunosuppressive medications are at risk. When CMV infection of the GI tract causes disease, symptoms include pain, ulceration, bleeding, diarrhea, and perforation. All levels of the GI tract, from the oropharynx to the anus, may be involved. Pathological examination of involved gut typically reveals diffuse ulcerations and necrosis with scattered CMV inclusions, although a variety of other abnormalities have been described. Before the introduction of antiviral therapy effective against CMV, mortality was high. However, the use of ganciclovir or foscarnet has improved the prognosis of CMV disease of the GI tract dramatically. CMV infection should be included in the differential diagnosis of GI disease in immunocompromised patients, and the clinician should pursue appropriate diagnostic and therapeutic interventions aggressively.