Reduction of infarct size as well as alleviation of other ischemia- and reperfusion-associated injuries are the goals of primary importance in cardiology. One of the remedies is considered to be myocardial preconditioning (PreCon) referred usually to as an increased myocardial tolerance to prolonged ischemia following brief ischemic or non-ischemic challenge. In this review, PreCon stimuli tested to date are considered including a number of mildly noxious factors applied either locally to the myocardium or systemically. Recently, one more mode of heart protection against reperfusion injury termed postconditioning (PostCon) has been developed. On the basis of ample evidence published, along with our findings, a detailed comparative analysis of PreCon and PostCon is presented, with special emphasis on the cellular, molecular, and pharmacological aspects of the topic as well as clinical applications, both implemented and awaiting practical approval.