BACKGROUND: The treatment of neuropathic pain continues to be difficult. Randomized, controlled trials (RCTs) provide some evidence to guide therapy. Most data relate to antidepressant therapy, although there is information on anticonvulsants and other treatments. Mistaken beliefs about many of these treatments are prevalent and need to be dispelled. Opioids are increasingly being used for the refractory patient. There has been recent enthusiasm for the anticonvulsant gabapentin for the treatment of these conditions.OBJECTIVE: To review the positive scientific data that are largely confined to RCTs in two neuropathic pain conditions that have proved to be good models for clinical investigation. These models are postherpetic neuralgia and painful diabetic neuropathy. Negative RCTs, weakly positive RCTs, other types of treatments and neuropathic conditions are also examined.METHODS: This review of the literature used MEDLINE, CINAHL and the Cochrane Database.RESULTS: There is extensive literature supporting the use of the older generation antidepressants, such as amitriptyline, in neuropathic pain. Newer RCTs support the use of gabapentin and opioids. Other therapies may be useful in individual cases on a trial and error basis but are largely unsupported by RCTs at this time.CONCLUSIONS: First-line therapy for neuropathic pain may be either an older generation antidepressant, such as amitriptyline or nortriptyline, or the anticonvulsant gabapentin. A variety of trial and error approaches may be used, none of which has sound scientific approval. For refractory patients, chronic opioid therapy may be the only avenue of relief, and evidence is accumulating that this approach is safe if proper guidelines are observed. The possibility that some types of neuropathic pain may be prevented is exciting. Progress in the treatment of neuropathic pain has been slow but steady, and there continues to be a need to explore newer agents and approaches.