OBJECTIVES Fibromyalgia (FM), a chronic disorder characterized by multiple symptoms (e.g., pain, fatigue, cognitive dysfunction, sleep disturbance), is difficult to treat. This study examined the extent to which FM patients in the US receive multiple prescription (Rx) drugs to treat their condition ("polypharmacy"). METHODS Using a large US health insurance database spanning a three-year period (January 1, 2005 to December 31, 2007), we identified all patients with ≥1 medical encounters for FM (defined as ICD-9-CM code 729.1) in each of these three calendar years ("FM patients"). Rx medications designated as possibly related to the treatment of FM ("FM-related") included antiepileptics, benzodiazepines, nonsteroidal anti-inflammatory drugs (NSAIDs), muscle relaxants, sedatives/hypnotics, opioids, selected antidepressants (e.g., tricyclics, serotonin-norepinephrine reuptake inhibitors, selective serotonin reuptake inhibitors), L-dopa, and carbidopa. Polypharmacy, which was defined as receipt of ≥2 FM-related Rx drugs, was assessed from two alternative perspectives: 1) period-prevalence (receipt anytime during each calendar year), and 2) point-prevalence (evidence of use on July 1 of each calendar year). RESULTS A total of 51,885 patients met all study entry criteria, of whom 33,831, 34,484, and 34,616 received FM-related Rx drugs in calendar years 2005, 2006, and 2007, respectively. The most commonly received Rx drugs were opioids, antidepressants, and NSAIDs. Among patients receiving FM-related Rx drugs, approximately 80% had evidence of receipt of ≥2 such medications in any given year; about 60% had evidence of receipt of 3 or more. Corresponding point-prevalence rates (on July 1 of each year) were approximately 61% and 36%, respectively. Commonly used combinations of Rx drugs included antidepressants and opioids, antiepileptics and antidepressants, and antiepileptics, antidepressants, and opioids. CONCLUSIONS Polypharmacy in the treatment of FM is widespread, suggesting that the symptoms of relatively few patients are well managed with any single currently available Rx drug.