In spite of improved myocardial protection, postoperative arrhythmias and cardiac failure are still important problems causing morbidity and mortality in cardiac surgery. Ischemic preconditioning has been widely investigated experimentally with the purpose of identifying new therapeutic agents, but we have not unraveled the underlying mechanisms and we are not able yet to exploit them pharmacologically in clinical practice. Studies of preconditioning in cardiac surgery provide conflicting results, but the majority of studies show that ischemic preconditioning is an effective adjunct to myocardial protection in cardiac surgery. Interventions aimed at modifying reperfusion, or postconditioning, have the advantage that they also can be used after the ischemic insult has occurred, i.e. also in situations with "non-scheduled" ischemia. Postconditioning, as preconditioning, needs pharmacological mimics to be used routinely in settings of cardiac surgery or other human interventions. Possible common signaling pathways of the two phenomena are discussed, and suggested directions for clinical studies are outlined.