The article examines the role of mitochondrial K_ATP channels in cardioprotection. The purpose of the study is to discuss the evidence which supports the role for the mito K_ATP channel in ischemic preconditioning and cardioprotection in the presence of K_ATP openers. Although it was fairly easy to predict a mechanism as to why opening the sarc K_ATP channel might produce cardioprotection based on its known properties to reduce calcium overload via membrane hyperpolarization and action potential shortening, it is less well understood how opening the mito K_ATP channel results in cardioprotection.