Few things have generated more excitement in the field of epilepsy than studies suggesting that N-methyl-d-aspartate (NMDA) receptors may play a role in the development and expression of seizures. It is possible that antagonists of the NMDA receptor channel complex may become a new class of anti-epileptic drugs which not only suppress seizures, but in some cases may be able to prevent the development of the epileptic condition altogether. Given the significance of the latter possibility, it is not surprising that the NMDA receptor has become the focus of intense study. A wealth of new pharmacologic agents has been developed that has facilitated a wide range of in vivo and in vitro studies. This chapter briefly reviews some of the earlier studies and then focuses on the large number of recent advances.