In the past several years, dramatic advances have been made in understanding the short- and long-term effects of alcohol on the central nervous system. These advances have provided new insight into the pathophysiology of alcohol withdrawal seizures. In contrast to epileptic seizures, alcohol withdrawal seizures originate in brainstem systems and involve unique cellular and molecular mechanisms. Older antiepileptic drugs, such as phenytoin and carbamazepine, are not useful in the prophylaxis of alcohol withdrawal seizures, and even benzodiazepines, the current mainstay of therapy in the United States, may not be optimal. Newer agents, such as chlormethiazole, topiramate, gabapentin, and valproate are promising, but validation in controlled clinical trials is necessary. The emerging understanding of the neurobiology of alcohol withdrawal suggests additional treatment approaches. For example, because NMDA-receptor antagonists are highly effective in animal models of alcohol withdrawal seizures (59) and, in addition, have antiepileptogenic activity in kindling models (90), it will be of interest to determine whether such agents will be clinically useful in prophylaxis against acute withdrawal seizures or in the kindling that occurs with multiple detoxifications.