Research into the causes of ischemic damage has evolved into an exploration of the brain's molecular responses. In attempting to discover the specific mechanisms by which ischemic cells die, a number of protective responses which are used by the cells to prolong or assure survival have also been understood, and some of these may become useful therapeutic tools. In this limited review, the mechanisms that are most likely to play a role in determining whether an ischemic cell survives or not are identified and examined. Particular emphasis is placed on the role of immediate early genes, heat shock proteins and trophic factors, and the more recent suspicion that cell cycle genes may be involved in the process of death by apoptosis. As well, the possibility that spreading depression may be a tool that may permit a better understanding of some of these mechanisms as well as offer new therapeutic avenues is examined.