From the clinical perspective, a continued analysis of the hippocampus in animal models of epilepsy as well as in human material will be critical to finally understanding MTLE. Through the continued evolution of surgical feedback to our preoperative localization studies, and from our basic science studies on resected tissue, we propose that 1) the hippocampus is critical to developing medial temporal lobe excitability, and that the inhibitory hilar interneurons which suffer most during developmental injury are likely to be involved in this process; 2) the hippocampus is not the only potentially hyperexcitable medial temporal lobe structure, but seems to function (both normally and pathologically) in a recurrent loop consisting of the entorhinal cortex, amygdala, and temporal neocortices; and 3) hypotheses derived from animal model studies, and data obtained directly from analysis of human tissue can be used to refine epilepsy classifications.