This last article in a three-part series on approved medications for managing fibromyalgia syndrome (FMS) reviews pregabalin (Lyrica ®). Pregabalin was the first drug approved for FMS management and, as an anticonvulsant, differs from the other approved agents that are antidepressants. Pregabalin inhibits presynaptic excitatory neurotransmitter release by blocking α 2δ calcium channels. Five randomized, placebo-controlled trials have demonstrated pregabalin reduces pain and improves sleep and health-related quality of life in FMS patients. While indicated dosing is 300–450 mg divided twice daily, initial dosing of 25–50 mg at night is recommended owing to side effects including somnolence, dizziness, and cognitive dysfunction. Since side effects such as weight gain and peripheral edema are dose-related, uptitration in weekly increments based on tolerability and therapeutic response is recommended. Due to its lack of protein binding and negligible hepatic metabolism, pregabalin can be safely combined with other medications and used in patients with renal failure when the dose is appropriate. Pregabalin may worsen sedation when combined with central nervous system depressants. Pregabalin should be discontinued gradually. Pregabalin-treated patients should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior. Pregabalin in combination with the other approved medications may be synergistic in treating FMS.