Patients suffering from chronic fatigue syndrome (CFS) are likely to show a premorbid overactive lifestyle. In this article the actual state of research on this issue is first summarized. It is further hypothesized that sociocultural, psychodynamic, cognitive, as well as psychobiological factors may mediate the relationship between overactivity and CFS. It is also argued that this lifestyle feature will often be a central focus in the cognitive-behavioural treatment and rehabilitation of CFS patients. Finally, some future research perspectives are outlined.