Experimental and human data have shown that certain seizures cause damage to brain. Such neuronal loss may result in cognitive impairments and perhaps contribute to the development or phenotype of emergent epilepsy. Recent work using genetically modified mice, Tat protein transduction, and viral vectors has shown functional effects of manipulating Bcl-2 and Bcl-w, heat shock proteins, caspases, and their regulators and endonucleases on neuronal death in models of status epilepticus. Ancillary effects on seizure induction and excitability thresholds have emerged for several genes suggesting additional properties of therapeutic potential. Differing hippocampal expression of certain Bcl-2 family genes, elevated endoplasmic reticulum stress chaperones, and death receptor pathway modulation in epilepsy patients support clinical relevance of this focus. These findings may yield potentially valuable adjunctive neuroprotective or anti-epileptogenic strategies.