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OBJECTIVE: Chronic fatigue syndrome is an illness characterized by disabling fatigue of at least 6 months, accompanied by several other symptoms. This review summarizes the current state of knowledge about chronic fatigue syndrome. METHOD: The case definition, prevalence, clinical presentation, evaluation, and prognosis of chronic fatigue syndrome are discussed. Research on the pathophysiology and treatment of chronic fatigue syndrome is reviewed. RESULTS: Chronic fatigue syndrome is diagnosed on the basis of symptoms. Patients with chronic fatigue syndrome experience significant functional impairment. Pathophysiological abnormalities exist across many domains, suggesting that chronic fatigue syndrome is a heterogeneous condition of complex and multifactorial etiology. Evidence also is beginning to emerge that chronic fatigue syndrome may be familial. Although chronic fatigue syndrome has significant symptom overlap and comorbidity with psychiatric disorders, several lines of research suggest that the illness may be distinct from psychiatric disorders. Patients’ perceptions, attributions, and coping skills, however, may help perpetuate the illness. Treatment for chronic fatigue syndrome is symptom-based and includes pharmacological and behavioral strategies. Cognitive behavior therapy and graded exercise can be effective in treating the fatigue and associated symptoms and disability. CONCLUSIONS: Chronic fatigue syndrome is unlikely to be caused or maintained by a single agent. Findings to date suggest that physiological and psychological factors work together to predispose an individual to the illness and to precipitate and perpetuate the illness. The assessment and treatment of chronic fatigue syndrome should be multidimensional and tailored to the needs of the individual patient.