This article reviews the current state of research in chronic fatigue syndrome (CFS). The evolving definition, prevalence, and prognosis of this controversial illness are presented. We review studies examining psychiatric, personality, and psychosocial etiology for CFS. The evidence for pathophysiology in CFS is also presented, and studies investigating viral, immune, neuroimaging, neuroendocrine, and central and autonomic nervous system abnormalities in CFS are assessed. Current evidence indicates that CFS is multi-determined and heterogeneous and that subgrouping patients according to factors such as psychiatric state and symptom onset may be fruitful. The current state of treatment for CFS is reviewed, and the challenges for research aimed at resolving this prototypical mind/body problem are discussed.