Ca2+ enters myocardial cells through a variety of pathways, including in exchange for Na+; by passive diffusion; through voltage-activated, gated channels; and in exchange for K+, Ca2+ entry through the voltage-activated channels is an essential step in excitation-contraction coupling. It is only this component of Ca2+ transport that is inhibited by the Ca2+ entry blockers. As a group, therefore, these drugs interfere with excitation-contraction coupling in heart but not in skeletal muscle. Accordingly they reduce the energy requirements of the heart. Their inhibitory effect on voltage-activated inward transport of Ca2+ into smooth muscle cells also results in dilation of the coronary vessels, with improvement in coronary perfusion, and of peripheral vessels, with after-load reduction. The resultant action of these drugs in maintaining myocardial energy balance and intracellular Ca2+ homeostasis is therefore complex, and tends toward preservation of myocardial structure and function after episodes of ischemia. Although the Ca2+ entry blockers prevent protein release and preserve ultrastructure in damaged myocardium, this is probably an indirect effect of their ability to impede slow channel transport of Ca2+.