Cytomegalovirus (CMV) has emerged as a significant opportunistic pathogen in the era of immunosuppression. CMV was a common cause of gastrointestinal disease in AIDS patients, but the introduction of highly active antiretroviral therapy has led to a dramatic decline in AIDS-related disease. Among patients with solid organ transplants, CMV has become an increasingly important cause of gastrointestinal disease as more routine use of early CMV prophylaxis has increased delayed-onset disease, which is often tissue invasive at presentation. The role of CMV in inflammatory bowel disease is controversial; treatment may be indicated in selected cases of steroid-refractory disease with evidence of CMV. Diagnosis of gastrointestinal CMV disease generally requires endoscopic biopsy with histologic confirmation. CMV culture of biopsy material may be falsely positive because of contamination from latently infected cells. The standard induction treatment of gastrointestinal CMV disease uses intravenous ganciclovir, though the use of oral valganciclovir is increasing, especially for long-term maintenance or suppression therapy.