Preconditioning the myocardium by brief repeated periods sub-lethal ischaemia evokes powerful endogenous mechanisms of cellular adaptation that can protect the myocardium against subsequent lethal ischaemia. The clinical exploitation of preconditioning in both pathological and surgical situations to ensure myocardial viability is attractive. Expansion in the knowledge of the mechanisms underlying preconditioning has brought us close to the threshold of developing useful therapies. In this review we critically appraise the research that has been thus far performed and review possibilities for the future.