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Despite decades of research and a half dozen new anticonvulsant agents, some types of seizures are as untreatable now as they were in the days of bromides. These treatment-resistant seizures suggest that some of the assumptions about anticonvulsant mechanisms may need revision. This review will focus on one of the bedrock assumptions of epileptology that the neurotransmitter GABA inhibits neuronal activity, and therefore, agents that increase GABA activity should increase inhibition and consequently decrease the abnormal neuronal activity that occurs during a seizure.