This structured review addresses the issue of whether antidepressants have an antinociceptive (analgesic) effect for chronic pain independent of their antidepressant effect. In order to answer this question, human acute pain studies, individual placebo-controlled studies for the treatment of specific chronic pain syndromes, and metaanalytic studies were reviewed and placed into table format. Analysis of this evidence led to the following conclusions: The evidence was consistent in indicating that overall antidepressants may have an antinociceptive effect in chronic pain, and that these drugs were effective for neuropathic pain. There was also some evidence that these drugs could be effective for psychogenic or somatoform disorder-associated pain. This evidence also strongly suggested that serotonergic-noradrenergic antidepressants may have a more consistent antinociceptive effect than the serotonergic antidepressants. Finally, this evidence indicated that antidepressants could be effective for pain associated with some specific pain syndromes, such as chronic low back pain, osteoarthritis or rheumatoid arthritis, fibrositis or fibromyalgia, and ulcer healing. Possible reasons for the conflicting results of studies in this area are presented, and problems that could limit the validity of the conclusions of this review are discussed.