Fibromyalgia syndrome (FMS) is a chronic multisymptom illness characterized by widespread pain and associated with neuropsychological symptoms including fatigue, unrefreshing sleep, cognitive dysfunction, anxiety, and depression. A discreet cause of FMS has not been identified. It is likely that multiple mechanisms give rise to symptom expression. Understanding specific etiologic factors and pathogenic mechanisms in individual patients will allow clinicians to determine treatments that are most effective for a given patient. Available evidence implicates the central nervous system as key in maintaining pain and other core symptoms of FMS. The approach to treatment of pain will typically address these central mechanisms. Nonpain symptoms may be treated by drugs affecting similar central neurochemicals. This paper will review the rationale for the different types of pharmaceutical treatments that may be useful for the treatment of FMS and issues regarding new drug development for this indication.