The Chronic Fatigue Syndrome (CFS) is described based on the revision of Fukuda et al. The question "whether CFS can be discussed as a homogenous disorder?" has been reviewed and the answer is "no". Other overlapping syndromes are mentioned. Disorders with fatigue as a symptom are depression, somatisation, irritable bowel syndrome, effort-syndrome, hyperventilation, conservation-withdrawal. Among the pathogenetic factors of CFS immune systems disorders, neuroendocrine abnormalities, autonomic activity, neuroimaging, neuropsychological abnormalities, exercise capacity and muscle function and psychological processes (attribution, perception, symptom avoidance and neutralisation of conflicts) are discussed. Since CFS cannot be comprehended without knowledge of the ontogenetic development of the affect "fatigue", it is extensively described. Based on this knowledge, fatigue as an affect and the CFS are embedded in a context, which has as its basis the fight-flight reaction and the conservation-withdrawal reaction. Weighing the evidence, it is concluded that CFS in its varieties can best be understood as a manifestation of the activation of the two biological emergency reactions: fight-flight and conservation-withdrawal. The physician should interview and examine each individual patient according to the Harvey Cushing dictum: The physician should not only study the diseased organ, but the man with his diseased organ, and not only these. He should comprehend the man with his diseased organ in his environment. This leads to study of the biological, psychological and social factors contributing to each patient's illness. Work-up and therapy have to be based on this integrated approach. The latter encompasses conflict centred psychotherapy, stepwise increasing physical activation and antidepressive drugs.