Neuropathic pain is a challenge for clinicians because it is resistant to commonly prescribed analgesics, such as opioids and nonsteroidal antiinflammatory drugs. Fortunately, adjuvant analgesics, drugs not typically thought of as pain relievers, may be effective. It is helpful to classify adjuvant analgesics used to treat neuropathic pain into two broad categories: (1) membrane stabilizing agents, which inhibit ectopic discharges on damaged neural membranes, and (2) drugs that enhance dorsal horn inhibition, which may augment biogenic amine or GABAergic mechanisms in the dorsal horn of the spinal cord. Current evidence regarding efficacy generally does not support the use of one drug over another, and selection of a particular drug may depend on experience or expected side effects. The overall efficacy of tricyclic antidepressants for neuropathic pain is modest, and they may produce intolerable side effects. Based on current studies, gabapentin is a reasonable alternative to antidepressants, as initial monotherapy or add-on treatment, particularly for painful diabetic peripheral neuropathy and postherpetic neuralgia. From a practical standpoint, to optimize analgesia more than one drug may be necessary. Although polypharmacy is the result, this approach may improve therapy and minimize side effects. From a safety standpoint, medications generally should be started at low doses and titrated to effect. Although labor-intensive, this strategy can improve compliance and optimize patient care.