Autophagy is a housekeeping process that helps to maintain cellular energy homeostasis and remove damaged organelles. In the heart, autophagy is an adaptive process that is activated in response to stress including acute and chronic ischemia. Given the evidence that autophagy is suppressed in energy-rich conditions, the objective of this review is to examine autophagy and cardioprotection in the setting of the metabolic syndrome. Clinical approaches that involve the induction of cardiac autophagy pharmacologically to enhance the heart's tolerance to ischemia are also discussed.