Most children with prolonged, recurrent, or periodic fever are healthy and have self-limited, common illnesses, and the primary care practitioner usually can reassure families and continue to reassess the patient as circumstances dictate. For a child with true fever of unknown origin, a pediatric infectious diseases subspecialist should be consulted. This article discusses three objectives for the clinician: (1) to categorize patterns of fever illnesses and prioritize differential diagnoses; (2) to diagnose and manage the most frequently encountered prolonged fever syndrome, deconditioning; and (3) to expand knowledge and approach to diagnosing periodic fever syndromes. The approach described in this article represents the honed, 30-year experience of a pediatric infectious diseases subspecialist.