The efficacy of gabapentin (GPT) and pregabalin (PGB) in the treatment of fibromyalgia syndrome (FMS) was assessed. We screened MEDLINE, PsycINFO, SCOPUS, www.clinicaltrials.org, the Cochrane Library (through October 2008), and the reference sections of original studies on GPT/PGB in FMS. Randomized controlled trials (RCTs) on the treatment of FMS with GPT and PGB were analyzed. Six out of 127 RCTs studying 2422 subjects on treatment with GPT (one study) or PGB (five studies) and 1056 subjects on placebo with a median treatment duration of 11 weeks were included into the systematic review. Five studies were suitable for meta-analysis. Effects were summarized using standardized mean differences (SMD). There was strong evidence for a reduction of pain (SMD -0.28, 95% CI −0.36, −0.20; p < 0.001), improved sleep (SMD −0.39, 95% CI −0.48, −0.39; p < 0.001), and improved health-related quality of life (HRQOL) (SMD −0.30, 95% CI −0.46, −0.15; p < 0.001), but not for depressed mood (SMD −0.12, 95% CI −0.30, 0.06; p = 0.18). There was strong evidence for a non-substantial reduction of fatigue (SMD −0.16, 95% CI −0.23, −0.09, p < 0.001) and of anxiety (SMD −0.18, 95% CI −0.27, −0.10; p < 0.001). The external validity of the studies was limited because patients with severe somatic and mental disorders were excluded.