Myocardial adaptation to ischemia in the form of ischemic preconditioning is clinically attractive, but not easily usable in cardiac surgery until molecular mimics are discovered. The various forms of pre- and postconditioning, including remote preconditioning, indicate that a 'universal' protection is evoked. A growing body of evidence indicates that events underlying myocardial adaptation to ischemia may either involve, or be parallel to, signaling of the innate immune response. The heart can be protected through giving cytokines or fragments of bacterial walls. A possible role for cytokines, Toll-like receptors, and nuclear factor kappa B for evoking ischemic preconditioning are discussed. Through stimulating innate immunity, there is potential to bring preconditioning into the clinics in a reasonable time frame. Other approaches to myocardial protection, using cell transfer, gene therapy, and microRNA, are briefly commented on.