Fibromyalgia (FM) falls into the spectrum of what might be termed 'stress-associated syndromes' by virtue of frequent onset after acute or chronic stressors and apparent exacerbation of symptoms during periods of physical or emotional stress. Patients with FM exhibit disturbances of the major stress-response systems, the HPA axis and the sympathetic nervous system. Integrated basal cortisol levels measured by 24-hour urine-free cortisol are low. FM patients display a unique pattern of HPA axis perturbation characterized by exaggerated ACTH response to exogenous CRH or to endogenous activators of CRH such as insulin-induced hypoglycaemia. The cortisol response to increased ACTH in these stress paradigms is blunted, as is the the cortisol response to exercise. Functional analysis suggests that FM patients may also exhibit disturbed autonomic system activity. For example, plasma NPY, a peptide co-localized with norepinephrine in the sympathetic nervous system, is low in patients with FM. Abnormalities of related neuronal systems, particularly decreased serotonergic activity, may contribute to the observed neuroendocrine perturbations in FM. Finally, other neuroendocrine systems, including the growth hormone axis, are also abnormal in FM patients. Many clinical features of FM and related disorders, such as widespread pain and fatigue, could be related to the observed neuroendocrine perturbations. This hypothesis is supported by the observation that many useful treatments for FM affect the function of these central nervous system centres. Further clarification of the role of neuroendocrine abnormalities in patients with FM, and the relationship of these disturbances with particular symptoms, may lead to improved therapeutic strategies.