Fibromyalgia is a common musculoskeletal pain disorder associated with mood disorders. Antidepressants, particularly tricyclics, are commonly recommended treatments. Randomized, controlled trials of antidepressants for treatment of fibromyalgia were reviewed by methodology, results, and potential predictors of response. Twenty-one controlled trials, 16 involving tricyclic agents, were identified; 9 of these 16 studies were suitable for meta-analysis. Effect sizes were calculated for measurements of physician and patient overall assessment, pain, stiffness, tenderness, fatigue, and sleep quality. Compared with placebo, tricyclic agents were associated with effect sizes that were substantially larger than zero for all measurements. The largest improvement was associated with measures of sleep quality; the most modest improvement was found in measures of stiffness and tenderness. Further studies are needed utilizing randomized, double-blind, placebo-controlled, parallel designs with antidepressants administered at therapeutic dose ranges, using standardized criteria for fibromyalgia and systematically assessed for co-occurring psychiatric illness.