Infectious mononucleosis caused by Epstein-Barr virus (EBV) usually resolves over a period of weeks or months without sequelae but may occasionally be complicated by a wide variety of neurologic, hematologic, hepatic, respiratory, and psychological complications. The strength of association of EBV with many of these complications remains based on scattered case reports, often using unsophisticated diagnostic tests, and the evidence for causation in many instances is unconvincing. There is little benefit of antiviral treatment of uncomplicated or complicated infectious mononucleosis. Corticosteroids may have a role in hastening resolution of some complications, especially upper airway obstruction and possibly immune-mediated anemia and thrombocytopenia, but should be used judiciously.