The aged heart has a diminished functional and adaptive reserve capacity, an increased susceptibility to incur damage (e.g., as a result of ischemia), and a limited practical ability for repair/regeneration. Thus, there has been considerable interest to harness the heart's endogenous capacity to resist such damage, known as ischemic preconditioning (IPC), as well as other cardioprotective mechanisms. However, the translation of basic research findings into clinical practice has largely been inadequate because there have been few if any successful implementations in terms of viable therapies activating cardioprotection mechanisms to limit infarct size. Here, we provide an overview of the general mechanisms of cardioprotection, changes in the structure and function of the aged heart, and the current knowledge regarding cardioprotection in aged heart. The problems and opportunities for successful bench-to-bedside translation of cardioprotection in the elderly are discussed.