ObjectiveTo outline the modes of action of topiramate and to examine the theoretical reasons as to why topiramate may alleviate neuropathic pain. Results of animal and human studies in the use of topiramate for treating pain are reviewed, together with case studies describing situations where topiramate was effective when other treatments have failed.ConclusionsTopiramate acts on neuronal transmission in at least five ways: by modulating voltage-gated sodium ion channels, potentiating &ggr;-aminobutyric acid inhibition, blocking excitatory glutamate neurotransmission, modulating voltage-gated calcium ion channels, and by inhibiting carbonic anhydrase. This review suggests that there are good theoretical reasons for a trial of topiramate in patients with neuropathic pain where conventional medical treatments have failed. Although not currently licensed for treating pain, topiramate should be considered before invasive methods of pain relief are contemplated. Most of the side effects of topiramate are dose dependent, but by starting medication with a low dose (≤25 mg/d) that is gradually titrated upward, tolerance is much more easily achieved.