The contributing roles of voltage-gated calcium channels (VGCC) to the generation of electrical signaling are well documented. VGCCs open in response to depolarization of the plasma membrane and mediate the flux of calcium into excitable cells, which further depolarizes the membrane. But a more relevant role of VGCCs is to serve as highly regulated mechanisms to deliver calcium ions into specific intracellular locales for a variety of calcium-dependent processes including neurotransmitter release, hormone secretion, neuronal survival, and muscle contraction. Recent biochemical and molecular biological studies have demonstrated that the calcium channel pore-forming subunit (alpha 1) is not an isolated entity, but in fact interacts physically with a variety of strategically localized proteins. The functional consequences of such interactions as well as other molecular aspects of VGCC will be discussed. Finally, although far from a final conclusion, what is currently known about the molecular composition of native calcium channels will be summarized.