<p>The views on myocardial ischemia are changing—with an increasing focus on plaque vulnerability in acute coronary syndromes and more attention to the coronary microcirculation in chronic coronary syndromes. The unifying paradigm of supply/demand mismatch to characterize myocardial ischemia was developed from experiments in dogs with coronary occlusion and reperfusion and later used to also characterize myocardial ischemia from stress- and exercise-induced ischemia in settings of epicardial coronary stenoses. However, the supply/demand paradigm of myocardial ischemia has fundamental problems and appears not well suited to explain clinical scenarios with coronary microvascular dysfunction. Demand is an anthropocentric/hypothetical parameter which cannot be measured. In fact, in detailed and extensive experiments in dogs and pigs, regional myocardial contractile function which largely determines energy consumption, is reduced proportionately with the reduction of blood flow during ischemia—there is a perfusion–contraction match. When coronary blood flow is expressed in µl/g per&#xa0;cardiac cycle, the relationships of flow and function in ischemic myocardium at rest and during exercise are superimposable. Supporting the view that flow determines function, beta-blockade increases blood flow per cardiac cycle and in consequence also increases contractile function of the ischemic myocardium rather than reducing its hypothetical demand. In acute coronary syndromes, again supporting the pivotal role of coronary blood flow, the only way to salvage ischemic myocardium is restoration of blood flow, and all maneuvers to protect ischemic myocardium such as ischemic conditioning work only in conjunction with reperfusion.</p>