For the clinician evaluating adolescents with chronic musculoskeletal pain and fatigue, the distinctions between JRA and FS are clear based on physical examination findings. The two conditions can coexist. For the patient with an initial diagnosis of either JRA or FS whose clinical response to therapy is not in keeping with expectations or physical examination findings or whose clinical course worsens without explanation, reevaluation to determine if FS in the JRA patient has developed or JRA in the FS patient has emerged is warranted. Until clinicians have a better understanding of the intricacies of the neurohormonal and immunologic systems and how they affect somatic symptoms, they can continue to provide patients with a treatment plan based on current knowledge that should minimize patients' discomfort and allow them to have appropriately functional lives.