Most children and adolescents who present with extremity pain in the emergency department (ED) have minor injuries or musculoskeletal problems that are easily diagnosed and managed. A history of a child or teenager with persistent extremity pain lasting more than a few weeks or pain that wakes the child at night is of clinical concern and requires investigation. There are serious clinical etiologies that must be included in the differential diagnosis of this group of patients. It is essential to take the time during the initial screening examination to determine the real reason for each patient ED visit and review previous medical care.