During the 1960s, it was observed that the tricyclic antidepressant imipramine was effective in the treatment of neuralgia, myalgia, and pain in carcinoma. Similarly, in other studies, clomipramine was also found to have an analgesic effect. The sedative antidepressant amitriptyline has proved effective in migraine prophylaxis, chronic tension headache, and psychogenic musculoskeletal and neuralgic facial pain. Controlled studies have also shown pain-relief in patients with postherpetic neuralgia and diabetic neuralgia. In cases of predominantly psychogenic headache, idiopathic trigeminal neuralgia and chronic neck and back pain, the sedative and anxiolytic antidepressant doxepin has been found to be an effective analgesic. As chronic pain patients are typically restless, irritable, and emotionally labile, sedative antidepressants tend to be prescribed in preference to stimulating drugs. Consequently, the compounds amitriptyline and doxepin have attracted increasing scientific interest in the field of algology. Nevertheless, our knowledge regarding the usefulness of these substances in treating chronic pain syndromes is incomplete in many areas. The remaining tricyclic and the tetracyclic antidepressants have not been sufficiently well evaluated. This is also true of monoamine oxidase inhibitors, of which individual reports to date suggest are probably also effective as analgesics. A scientific investigation into the possible differences in the effectiveness of various antidepressants in specific chronic pain conditions is an important task for the future.