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Voltage-gated Ca²⁺ (Ca_V) channels are found in all excitable cells and many nonexcitable cells, in which they govern Ca²⁺ influx, thereby contributing to determine a host of important physiological processes including gene transcription, muscle contraction, hormone secretion, and neurotransmitter release. The past years have seen some significant advances in our understanding of the functional, pharmacological, and molecular properties of Ca_V channels. Molecular studies have revealed that several of these channels are oligomeric complexes consisting of an ion-conducting α₁ subunit and auxiliary α₂δ, β, and γ subunits. In addition, cloning of multiple Ca_V channel α₁ subunits has offered the opportunity to investigate the regulation of these proteins at the molecular level. The regulation of Ca_V channels by intracellular second messengers constitutes a key mechanism for controlling Ca^{2 +} influx. This review …