Preconditioning is in experimental studies the most powerful mode of cardioprotection known. The signal transduction pathways involve a variety of trigger substances, mediators, receptors, and effectors. The studies of preconditioning in cardiac surgery provide conflicting results but the majority of studies show that ischemic preconditiong is an effective adjunct to myocardial protection. However, ischemic preconditioning with repeated clamping of the aorta will never get widespread use. If the "preconditioning response" is to be exploited in cardiac surgery, targeting the underlying molecular mechanisms must provide easily applicable techniques or drugs, which are shown in large scale clinical studies to be beneficial.