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Nociceptive pain serves the useful purpose of alerting the body to potential or actual tissue damage. By contrast, neuropathic pain that results from injury or damage to the nervous system persists long after all signs of the original injury have disappeared. Neuropathic pain presents a significant clinical problem as it responds poorly to classical analgesics such as non-steroidal anti-inflammatory drugs (NSAIDs) and to opioids; there is also no single, uniformly well-tolerated drug that is reliably helpful. Treatment currently involves the use of anticonvulsant and/or antidepressant drugs. Electrophysiological experiments on dorsal root ganglion and spinal cord neurons of nerve-injured experimental animals are yielding new information on the pathophysiology of neuropathic pain. Analysis of actions of various neuropeptides and neurotransmitters in these models has helped to explain the poor efficacy of opioids and suggests new therapeutic approaches to the management of neuropathic pain. Drugs that stimulate α2-c-adrenoceptors or that mimic the actions of neuropeptide Y, galanin, or the opioid-like peptide, nociceptin, may be of use in this regard. Drug Dev. Res. 54:140–153, 2002. © 2002 Wiley-Liss, Inc.