Numerous studies support the hypothesis that reperfusion following cerebral ischemia contributes substantially to ischemic injury and that mitochondrial dysfunction plays a central role. Defining the mechanisms by which mitochondrial dysfunction occurs may be important for the development of new therapies against delayed neuronal cell death. Ischemic preconditioning (IP) increases an organ's resistance to ischemic injury. There are two windows for IPC, one that requires several hours to develop and another one with a rapid setting (rapid window). However, the rapid window only provides neuroprotection for few days. We have recently determined that this lack of chronic protection by the rapid window was due to lack of protection against mitochondrial dysfunction.