The beneficial effects of calcium-entry blockers in the treatment of ischemia in the heart and in other tissues can be explained by (1) relaxation of venous smooth muscle, in particular that of the splanchnic veins; (2) negative inotropic effect on the myocardial cells; (3) negative chronotropic effects on the heart; (4) inhibition of vasospastic episodes in coronary and other large arteries; (5) depression of myogenic activity and responsiveness to vasconstrictor stimuli in precapillary resistance vessels; (6) inhibition of platelet aggregation; (7) possible increases in the deformability of hypoxic red blood cells; (8) protection of endothelial integrity and function; and (9) protection of the body cells, in particular myocardial cells, from prolonged exposure to anoxia and from massive entry of calcium during reperfusion. In the case of angina pectoris, the effects on the myocardial cells themselves, the decrease in preload and afterload, and the improvement of coronary perfusion combine to allow the heart to perform more work before an imbalance is reached between the metabolic demands of the myocardial cells and their blood supply. The increased myocardial performance may favor collateral circulation and withdrawal of the reflex load upon the heart, originating from the ischemic myocardium. The available calcium-entry blockers vary in their potency to affect the different components of the cardiovascular system.