Neuropathic pain results from a variety of medical conditions encountered in physiatric practice, including infection, trauma, metabolic abnormalities, and nerve compression. Unlike pain resulting from nociceptive or inflammatory processes, neuropathic pain is associated with primary lesion or dysfunction of the nervous system itself and is often difficult to treat. Existing treatment options include drug therapy (e.g., anticonvulsants, the lidocaine patch 5%, antidepressants, opioids, tramadol) or interventional treatments (e.g., peripheral or neuraxial nerve blockade, implanted spinal cord stimulators, implanted intrathecal catheters). The following article presents an overview of the cellular mechanisms associated with neuropathic pain, summarizes the results of randomized, controlled trials with the major classes of available drugs, and discusses treatment options that provide a rational basis for pharmacotherapy.