We report a case of chronic abdominal pain with subsequent development of acute right lower quadrant tenderness in a patient infected with the human immunodeficiency virus. Ultrasonography and computed tomography revealed an enlarged appendix. On subsequent laparotomy, the patient was found to have appendicitis due to cytomegalovirus. Six additional cases of this infection were identified in a review of the literature. The course of cytomegalovirus appendicitis in these patients was prolonged and atypical compared with noncompromised patients with acute appendicitis. Because perforation may occur, surgery is advocated when this diagnosis is suspected in the patient infected with human immunodeficiency virus.