Infectious mononucleosis, a systemic illness caused by the Epstein-Barr virus, is seen frequently by primary care physicians. Mononucleosis affects several organ systems, and, within the abdomen, there can be splenic involvement, hepatitis, mesenteric lymphadenopathy, hyperplasia of gut-associated lymphoid tissue, pancreatitis, and transient malabsorption. Life-threatening abdominal complications require prompt recognition and intervention. Other abdominal complications, though worrisome, are usually short-lived and resolve without sequelae.