Milnacipran is an orally administered selective serotonin and norepinephrine (noradrenaline) reuptake inhibitor indicated for the management of fibromyalgia in adults. In adults, milnacipran was generally effective in the treatment of fibromyalgia in four well designed trials of 3 or 6 months' duration. Composite responder rates for the treatment of fibromyalgia and fibromyalgia pain (co-primary efficacy variables) were generally higher with milnacipran 100 or 200 mg/day (in two divided doses) than with placebo after 12 weeks of fixed-dose treatment. In one study, the composite responder rate for fibromyalgia pain (co-primary efficacy variable) was also higher with milnacipran 200 mg/day than with placebo after 24 weeks of fixed-dose treatment. Furthermore, the benefits of milnacipran therapy were sustained in a 6-month extension of an initial double-blind trial. Improvements from baseline in mean 24-hour recall pain scores, mean weekly recall pain scores, Patient Global Impression of Change scores and in several items of the Fibromyalgia Impact Questionnaire were observed in patients receiving continuous milnacipran for up to 12 months, as well as in patients who switched from placebo to milnacipran therapy at the start of the extension phase. Milnacipran was generally well tolerated in adults with fibromyalgia, with most adverse events being mild to moderate in severity. Nausea was the most common adverse event reported in milnacipran recipients.