This article provides a critical review of the psychological and related literature on fatigue resulting in both mental and physical experiences. On one hand, prolonged severe fatigue is a prominent disabling symptom in various diseases of different aetiology – psychiatric (e.g. depression), somatic (e.g. some infections) and neurologic (e.g. multiple sclerosis, myasthenia gravis). For instance, fatigue is a main symptom of myasthenia that leads to pathological skeletal muscle weakness. Furthermore, 40 to 90 per cent of individuals suffering from multiple sclerosis confirm they have experienced fatigue, which impairs their cognitive functioning. In both multiple sclerosis and myasthenia, fatigue has not only a physical but also a psychological dimension. On the other hand, fatigue can be seen as an isolated set of symptoms of unknown origin called the chronic fatigue syndrome (CFS). The development of the concept, diagnostic criteria and some strategies of coping with CFS are presented. Various somatic disorders, as well as subjective cognitive and emotional complaints, are common and well documented in patients with CFS. The most typical include depression, as well as problems with concentration of attention, decision-making and reasoning in complex situations. However, general intellectual abilities and higher order cognitive skills are intact. Directions for future research are outlined.