Fibromyalgia (FM) is a chronic widespread pain condition that is estimated to affect 5 million US adults. Several molecular pathophysiologies are thought to contribute to the symptoms of FM, complicating the development of effective clinical management techniques. It is now known that abnormalities in both nociceptive and central pain processing systems are necessary (but perhaps not sufficient) to condition the onset and maintenance of FM, producing associated neuropsychologic symptoms such as pronounced fatigue, sleep abnormalities, cognitive difficulties, stress sensitivity, anxiety, and depression. Current treatment strategies are focused primarily on correcting the pathophysiologic mechanisms underlying these nervous system abnormalities. Clinical studies demonstrate the safety and efficacy of three drugs recently approved for the treatment of FM: pregabalin (an alpha-2-delta ligand), and duloxetine and milnacipran (serotonin/norepinephrine reuptake inhibitors). This review describes these pharmaceuticals in detail and discusses their current roles in FM management.