Digitalis is a potent inhibitor of sarcolemmal sodium (Na<sup>+</sup>), potassium (K<sup>+</sup>)-ATPase, and, through this property, effects net movement of calcium (Ca<sup>++</sup>) into the myocardial cell. Augmented contractility probably directly results from increased concentrations of activator Ca<sup>++</sup> available to the contractile elements. The clinical manifestations of digitalis toxicity are due to intracellular K<sup>+</sup> depletion, which is an obligatory consequence of Na<sup>+</sup>, K<sup>+</sup>-ATPase inhibition.Digitalis, as a positive inotropic agent, also augments myocardial energy consumption in the nonfailing heart. However, when digitalis is employed in the enlarged, failing heart, a simultaneous reduction in the intramyocardial tension leaves net myocardial oxygen balance unchanged or improved. Digitalis has no unique effect on myocardial energy metabolism. Digitalis acutely increases peripheral vascular resistance in man. Through sympathetically mediated responses, digitalis dilates peripheral blood vessels in patients with heart failure. The direct action of digitalis on the coronary vascular bed is uncertain. In ischemic heart muscle, digitalis can improve contractility, but at a metabolic price. The extent to which myocardial energy balance is affected depends on the simultaneous effect of digitalis on all determinants of myocardial oxygen consumption. Similarly, the hemodynamic changes effected by digitalis are not completely predictable because of many variables changing simultaneously, but generally reflect improved ventricular function. Studies in the dog indicate that the cardiovascular response to digitalis after myocardial infarction is a function of the particular time it is administered during recovery. Initial insensitivity is regained within one weeks’ time. Acute intravenous injections of digitalis in patients with myocardial infarctions may increase after load, thus offsetting the anticipated increase in stroke volume due to the change in contractility alone.The use of digitalis after uncomplicated myocardial infarctions is not recommended. Patients with clinical evidence of heart failure are likely to benefit from digitalis. The larger the heart size and the greater the time passed after the acute infarction when digitalis is administered, the better will be the response. No data presently available clearly demonstrate the efficacy of digitalis in patients with cardiogenic shock.