Patients with unexplained chronic pain and/or fatigue have been described for centuries in the medical literature, although the terms used to describe these symptom complexes have changed frequently. The currently preferred terms for these syndromes are fibromyalgia and chronic fatigue syndrome, names which describe the prominent clinical features of the illness without any attempt to identify the cause. This review delineates the definitions of these syndromes, and the overlapping clinical features. A hypothesis is presented to demonstrate how genetic and environmental factors may interact to cause the development of these syndromes, which we postulate are caused by central nervous system dysfunction. Various components of the central nervous system appear to be involved, including the hypothalamic pituitary axes, pain-processing pathways, and autonomic nervous system. These central nervous system changes lead to corresponding changes in immune function, which we postulate are epiphenomena rather than the cause of the illnesses.