Significant advances have been made over the past few years concerning the cellular and molecular events underlying ischemic cell death. The brain succumbs to ischemic injury as a result of loss of metabolic stores, excessive intracellular calcium accumulation, oxidative stress, and potentiation of the inflammatory response. Neurons can also die via necrotic or apoptotic mechanisms, depending on the nature and severity of the insult. While it has been widely held that ischemia is notable for cessation of protein synthesis, brain regions with marginal reduction in blood supply are especially capable of expressing a variety of genes, the functions of many of which are only beginning to be understood. Gene expression is also upregulated upon reperfusion and reoxygenation. As a result, a number of signaling pathways have been identified and are now known to contribute to ischemic progression or, in some cases, attempts at self preservation. This review will focus on the roles of stress genes, apoptosis-related genes, and inflammation. Knowledge of such molecular events has fueled interest in developing specific molecular targets with the hope of someday affecting outcome in clinical stroke.