Progress in cardiovascular disease understanding and management continues at an exponential pace. Our understanding of the molecular basis of disease is enhanced by newer molecular measurement techniques, sophisticated models of physiological protein functions, understanding of the genetic foundation for diseases, and the incorporation of population genetic tools in our clinical analysis. In this review, I discuss prevention and therapy of coronary stenosis impeding coronary flows, prevention of acute and chronic manifestation of coronary flow impairment, and interfering with myocardial manifestation of acute or chronic deprivation of coronary flow. Mechanical heart failure and arrhythmias are common causes of myocardial dysfunction that originate, in part, from the loss of myocardial tissue and function. Techniques for interfering with cardiac function, in order to address the molecular mechanisms associated with restenosis, range from pharmacologic to mechanical procedures including mechanical dilation and scaffolding of coronary stenosis. The use of stents with and without drug coating is leading the clinical world of revascularization side-by-side with cardiac bypass surgery. Other topics that are discussed here include managing myocardial damage and acute and chronic pump failure. Finally, population genetics of cardiac health and the potential for genetic therapeutic guidance in managing ischemic cardiovascular diseases are discussed.