This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the authors' clinical recommendations. The case: A 16-year-old, previously healthy girl presents with a several-day history of fever, sore throat, and malaise. She appears very tired and has a temperature of 39°C. A physical examination is remarkable for diffuse pharyngeal erythema with moderately enlarged tonsils and the presence of several enlarged, tender anterior and posterior cervical lymph nodes. How should this case be managed?