Fibromyalgia (FM) is a chronic pain syndrome characterized by widespread pain, fatigue, sleep alterations, and distress. Emerging evidence points toward augmented pain processing within the central nervous system as having a primary role in the pathophysiology of this disorder. Recent studies have identified distinct FM subgroups on the basis of clinical, neurochemical, and neuroendocrinological abnormalities, including increased cerebrospinal fluid levels of substance P and excitatory amino acids and functional abnormalities in the hypothalamic–pituitary–adrenal axis, and sympathoadrenal (autonomic nervous) system. Pharmacological treatments have been gradually enriched by a variety of compounds. Antidepressants, nonsteroidal anti-inflammatory drugs, opioids, sedatives, muscle relaxants, and alpha2-delta agonists have all been used to treat FM with varying results. Physical exercise and multimodal cognitive-behavioral therapy seem to be the most widely accepted and beneficial forms of nonpharmacological therapy. Studies predicting treatment response indicate that it is useful if not essential to tailor the choice of treatment components to the needs of individual patients.