Abstract: Refractory neuropathic pain can be devastating to a patient's quality of life. Ideally, the primary goal of therapy would be to prevent the pain, yet even the most appropriate treatment strategy may be only able to reduce the pain to a more tolerable level. Pharmacotherapy is currently the mainstay of treatment in patients with neuropathic pain, although at present the drugs are used on a mainly “off-label” basis. A wide variety of agents are used, especially antidepressants (ie, tricyclic antidepressants, selective serotonin-reuptake inhibitors) and anticonvulsants, but also opioids and tramadol, topical agents (eg, lidocaine), systemic local anesthetics, and anti-inflammatories. Even so, effective pain relief is achieved in less than half of patients with chronic neuropathic pain. In refractory patients, combination therapy using two agents with synergistic mechanisms of action may offer greater pain relief without compromising the side-effect profile of each agent.