Antidepressants have been successfully used for chronic pain syndromes for approximately 30 years. One theory is that analgesic action is secondary to the antidepressant effects of the medications. Placebo-controlled trials have documented that antidepressants treat neuropathic pain, musculoskeletal pain, chronic pain, and cancer pain. The most frequently studied antidepressant for pain is amitriptyline. Other antidepressants that have shown analgesic activity include imipramine, citalopram, paroxetine, nortriptyline, desipramine, and mianserin. Fluoxetine and trazodone have not been shown to successfully treat pain syndromes. Venlafaxine, a new antidepressant, most recently was shown to have antidepressant activity in fibromyalgia. More studies need to be done with newer antidepressants to confirm their place in treating pain syndromes.