Pharyngitis or sore throat is a common result of illness in pediatric and adolescent populations. Sore throat can signal either nonsystemic or systemic disease processes. Clinicians in ambulatory settings are often faced with deriving a differential diagnosis based on this symptom. Prompt and appropriate treatment depends on identification of the underlying causative agent or illness. This article examines common causes of sore throat in the pediatric and adolescent populations. These diagnoses are: (1) group A beta-hemolytic streptococcal pharyngitis; (2) non-group A beta-hemolytic streptococcal bacterial pharyngitis; (3) viral pharyngitis; (4) infectious mononucleosis; and (5) chronic conditions. Less common causes are also considered. Differential diagnosis Is dependent on complete and accurate history, distinct physical finding, and interpretation of adjunct diagnostic tests. The value of critical data sources Is essential in arriving at a differential diagnosis of pharyngitis. Once a diagnosis is established, an appropriate treatment plan can be initiated.