A molecular explanation for why some neurons are more vulnerable than others to ischemic injury has long remained elusive. In this issue of Neuron, Peng et al. propose that CREB-dependent downregulation of the RNA editing enzyme ADAR2, resulting in defective Q/R editing of AMPA receptor GluR2 subunits and increased availability of calcium and zinc-permeable death-promoting AMPA receptors, underlies the vulnerability of some neuronal populations to ischemia.