For many years, tricyclic antidepressants (TCAs) were used as initial therapy for the pharmacologic management of neuropathic pain. First-generation antiepileptic drugs (AEDs) are also used for the treatment of pain, and two drugs in this group, carbamazepine and sodium valproate, have received FDA approval for trigeminal neuralgia and migraine headache, respectively. Although TCAs are associated with side effects that limit their usefulness, particularly in the elderly or in patients with multiple medical problems, comparative meta-analyses show their tolerability to be greater than that of the first-generation AEDs. Recently, newer AEDs with more favorable side-effect profiles have been tested in placebo-controlled clinical trials for the treatment of neuropathic pain, including painful diabetic neuropathy and postherpetic neuralgia. The results of these trials, together with advances in understanding the pathophysiology of neuropathic pain, provide the basis for reevaluating some of the commonly accepted paradigms that guide approaches to treatment.