The cardinal features of fibromyalgia are chronic widespread pain in the presence of widespread tenderness as measured by multiple tender points. Despite extensive investigations, the etiology of this syndrome remains unclear. Increased rates of psychiatric disorders, particularly depressive, anxiety, and somatoform disorders, are apparent in clinic populations. Epidemiologic evidence suggests that this is also true for community subjects. Depression, generalized psychological distress, and other psychological factors have been shown to be associated with the onset and persistence of fibromyalgia symptoms. However, the bodily processes through which such factors may lead to the onset of fibromyalgia are unclear. Recent investigations have demonstrated altered stress system responsiveness, most notably the hypothalamic-pituitary-adrenal stress axis, in patients with fibromyalgia. These findings, and one promising avenue for investigating the interaction between psychological and biological factors in the onset of chronic pain syndromes including fibromyalgia, are discussed.