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Fibromyalgia syndrome (FMS) is defined by the presence of chronic, widespread pain and tender points. Research implicating hypersensitization of central neural pathways in the pathogenesis of FMS pain has led to the development of medications that treat FMS by modulating synaptic activity, including duloxetine, milnacipran and pregabalin-all of which have undergone successful clinical trials. Duloxetine and milnacipran are selective norepinephrine and serotonin reuptake inhibitors that improve pain by increasing the activity of antinociceptive pathways. Pregabalin is an α2δ calcium channel antagonist that reduces pain by limiting the release of excitatory neurotransmitters. While treatment of FMS pain is important, effective FMS management requires identification and treatment of all symptoms experienced by individual FMS patients, which can include fatigue, insomnia, depression and anxiety. Unfortunately, the lack of standardization in FMS trial design and controversy surrounding the disorder have complicated the development of integrated therapeutic regimens that could bring about a brave new world of effective management of FMS.