The synthetic opioid methadone has generated much interest in recent years among clinicians involved in the management of intractable chronic cancer pain. Its use as an analgesic is starting to extend to the treatment of noncancer pain, particularly neuropathic pain. Unfortunately, the evidence for its use in the management of neuropathic pain is limited to a few case studies. We examined retrospectively during a 12-month study period the clinical response of all 13 patients at our pain clinic who were prescribed methadone in an attempt to control neuropathic pain resistant to conventional analgesics. A questionnaire was also administered to the 9 patients who continued to take methadone at 12 months posttreatment. A total of 4 patients (31%) discontinued it by the end of the 12-month study period. Patients discontinued methadone due to the absence of pain relief and due to various intractable, undesirable side effects. Somnolence was the most common adverse effect reported, followed by nausea, constipation, and vomiting. All patients took coanalgesics (eg, amitriptyline, gabapentin) or other analgesics (eg, morphine, nonsteroidal anti-inflammatory drugs) during methadone treatment to control pain. The 9 patients who continued to take methadone at 12 months reported experiencing on average 43% pain relief (range 0-80%), 47% improvement in quality of life (range 0-100%), and 30% improvement in quality of sleep (range 0-60%). Methadone was effective at relieving pain and ameliorating quality of life and sleep in 62% of patients. These findings suggest that methadone can offer an acceptable success rate for the treatment of neuropathic pain. Prospective randomized, placebo-controlled studies are now needed to examine more rigorously the benefits of methadone for this type of pain.