Milnacipran hydrochloride is a serotonin (5-HT) and norepinephrine (NE) reuptake inhibitor that was recently approved by the US FDA for the treatment of fibromyalgia (FM). Evidence has accumulated suggesting that, in animal models, milnacipran may exert pain-mitigating influences involving norepinephrine- and serotonin-related processes at supraspinal, spinal and peripheral levels in pain transmission. Milnacipran has demonstrated efficacy for the reduction of pain as well as improvements in global assessments of well-being and functional capacity among treated FM patients. Its role in addressing comorbidities associated with FM, including visceral pain and migraine, has, as yet, to be investigated. Milnacipran may be of special interest for use in patients for whom hepatic dysfunction precludes the use of other agents, for example, duloxetine. It has a negligible influence on cytochrome metabolism, and therefore may be of particular benefit in patients requiring multiple concurrently prescribed medicatio...