Cases of long-standing (6 months or longer) fatigue that are not explained by an existing medical or psychiatric diagnosis are referred to as chronic fatigue syndrome (CFS). CFS is a condition of unknown etiology that presents with a complex array of symptoms in patients with diverse health histories. A diagnosis of CFS is largely dependent upon ruling out other organic and psychologic causes of fatigue. CFS can present the clinician with a unique set of challenges in terms of diagnosis and treatment. A review of recent research suggests that the management of CFS requires an individualized approach for each patient. An historic overview of the condition is presented along with current theories of causation, diagnosis considerations, symptom management, and health promotion strategies.