Background　Large-conductance Ca2+-activated K+ channels(BKCa) may be important targets for therapeutic interventions in a variety of cardiac conditions.　Objective　This mini-review focuses on the modulation of cardiomyocyte BKCa channels for cardioprotection and briefly address associated potential therapeutic benefits in the coronary circulation.　Content　In cardiomyocytes, BKCa channels are localized to mitochondria where they beneficially modulate reactive oxygen species, mitochondrial Ca2+, and respiration. In vascular smooth muscle cells, BKCa channels regulate vascular tone and promote vasodilation.　Trend　Activation of BKCa channels has demonstrated significant cardioprotection following ischemic injury, including improving myocardial function and reducing infarct size.