Functional consequences of myocardial or cerebral infarction are the result of excessive cell death. It is patent that preventing cell death is the therapeutic goal in any ischemia-reperfusion setting. Mitochondria amplify apoptotic cascades and have emerged as crucial organelles in ischemia-reperfusion. Changes in mitochondrial inner membrane permeability and in the morphology of the organelle are regulated, perhaps interconnected processes that are starting to emerge as novel therapeutic targets for reducing cell death induced by ischemia-reperfusion.