Coronary artery disease is the leading causes of morbidity and mortality in man worldwide. Substantial efforts have been dedicated toward improvement of functional recovery and reduction of the extent of infarction after ischemic states. The mitochondrial adenosine triphosphate (ATP)- sensitive potassium channels (mito KATP) is the receptor for KATP channel openers (KCOs) that have been reported to possess protective role against various cardiovascular complications. Several experimental studies have shown a wide range of possible clinical uses of KCOs as bronchodilators, vasodilators and bladder relaxants. In addition, KCOs show various cardioprotective effects against arrhythmias, angina and heart failure. The present article highlights on the physiologic properties and functions of mito KATP channels in the cardiovascular system and on the role of the KCOs in the treatment of various cardiovascular complications.