The term "chronic fatigue syndrome" (CFS) applies to a condition of unknown aetiology characterized clinically by an association of subjective symptoms, the most constant being an invalidating tiredness. The diagnostic criteria in current use do not permit to isolate an homogeneous subgroup among patients consulting for chronic asthenia. In the present state of research no infectious or immunological cause has been demonstrated conclusively, although a persistent enterovirus or herpesvirus type 6 infection or a state of chronic immune activation seem to play a role in some cases. Patients who fulfill the criteria of CFS present with psychiatric overmorbidity, essentially depressive, and in 50% of the cases with the mental disorders preceding CFS. The various theoretical models linking CFS to psychopathology are discussed, and finally the syndrome is regarded as a social construction reproducing or renovating the neurasthenia of the late 19th century. There is no specific treatment of CFS, but antidepressants, cognitive-behavioural therapy and perhaps certain immuno-modulators can be useful. The future lines of research should endeavour to isolate a subgroup of patients with prolonged asthenia after a recognized episode of infection and to identify the immunological, psychological and behavioral characteristics of this particular group as well as their reciprocal interactions.