In both types of striated muscle (skeletal and cardiac), calcium flux across the plasma membrane (sarcolemma) is regulated by at least three distinct membrane proteins; a voltage-dependent Ca2+channel, Ca2+pump (Ca2+ATPase), and the Na+/Ca2+antiporter. Each of these proteins is subject to regulation by intracellular second messengers. The magnitude and the role of this transsarcolemmal calcium flux are quite different between cardiac and skeletal muscle. In cardiac muscle, the influx is large, precedes, and is obligatory for contraction. There is general agreement that this influx is the trigger for Ca2+release from the sarcoplasmic reticulum (SR) in the heart according to the Ca2+-induced Ca2+release hypothesis. Variations in the transsarcolemmal Ca2+influx have a profound effect on the strength of cardiac contraction, and it appears that this is the primary physiological strategy for regulation of contractility. In skeletal muscle, on the other hand, the T-tubules represent the richest source of dihydropyridine (DHP)-sensitive calcium channels known to exist, yet the influx of Ca2+is proportionally much smaller and a significant portion enters the fiber following the twitch. While the majority of the Ca2+influx is twitch dependent, it is quite clear that contraction in skeletal muscle is not predicated on this influx. It has been proposed that these DHP channels act as voltage sensors in order to initiate release of SR Ca2+; however, the link between the sensors and the opening of the SR Ca2+(ryanodine-sensitive) channel is unknown. Transsarcolemmal Ca2+transport appears to be subject to intense regulation to modify the acute response and demonstrates some plasticity in the adaptation to chronic perturbations.