Fibromyalgia is marked by high interpatient variability in both clinical course and efficacy of particular therapies. Fibromyalgia pain does not result from peripheral nociceptor stimulation but instead arises from deficient CNS processing and modulation of pain signals. Tricyclic antidepressants (TCAs) and related drugs have some efficacy when compared with placebo in clinical trials. In addition to TCAs and antidepressants, the other commonly seen approach to treating fibromyalgia pain is the use of anticonvulsants. In fibromyalgia patients taking long-term opioids, a methodologically rigorous study shows that administration of the non-ergot dopamine agonist pramipexole significantly reduces pain and improves myriad quality-of-life indices. The benzodiazepines are also associated with mixed results in fibromyalgia trials. Given the lack of inflammatory pathophysiology in fibromyalgia, it is not surprising that no data support use of corticosteroids or NSAIDs in treating fibromyalgia pain.