Ischemic injury to the myocardium is a leading cause of morbidity and mortality around the globe. It is worth remembering, however, that this insult to the heart emerged only in the last few centuries, an instant in time from an evolutionary perspective. Thus, any cardioprotective responses to ischemic injury undoubtedly evolved for an entirely different purpose. Beyond pure academic interest, however, there is a profound clinical need to identify new means of protecting the myocardium from disease-related stress. Among the strategies in development is a concerted effort to understand and enhance the body’s innate mechanisms of cardioprotection.