Chronic fatigue syndrome (CFS) is a medically unexplained illness characterized by chronic, disabling fatigue, impaired concentration, muscle pain, and other somatic symptoms. The conceptual difficulties associated with all medically unexplained illnesses contribute to the controversy surrounding CFS, which has centered around whether it is best regarded as a medical or as a psychiatric condition. Clinically, such an approach is not helpful, and current research suggests that both pathophysiologic changes and psychosocial factors are important. Pragmatic management based on a detailed assessment of the individual is outlined.