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Chronic Fatigue Syndrome (CFS) emerged as a diagnostic category during the last decade. Initial research suggested that CFS was a relatively rare disorder with a high level of psychiatric comorbidity. Many physicians minimized the seriousness of this disorder and also interpreted the syndrome as being equivalent to a psychiatric disorder. These attitudes had negative consequences for the treatment of CFS. Both the CFS case definition criteria and biases in the scoring and selection of psychiatric tests contributed to eliciting high rates of psychiatric comorbidity as well as the possibility of misdiagnosing purely psychiatric cases as CFS cases. In addition, early CFS epidemiological studies, which were based on physician referrals for case ascertainment, underestimated the prevalence of this illness. By the mid 1990’s, findings from more representative epidemiologic studies indicated considerably higher CFS prevalence rates. However, the use of the revised CFS case definition might have produced heterogeneous patient groups, possibly including some patients with pure psychiatric disorders. This development complicated the interpretation of epidemiologic data and treatment outcome studies, which currently recommend fundamentally distinct and conflicting rehabilitation programs. Social scientists have the expertise to more precisely define this syndrome and to develop appropriate and sensitive research strategies for understanding this disease.