Voltage-gated Ca²⁺ channels mediate Ca²⁺ entry into cells in response to membrane depolarization. Electrophysiological studies reveal different Ca²⁺ currents designated L-, N-, P-, Q-, R-, and T-type. The high-voltage-activated Ca²⁺ channels that have been characterized biochemically are complexes of a pore-forming α₁ subunit of ∼190–250 kDa; a transmembrane, disulfide-linked complex of α₂ and δ subunits; an intracellular β subunit; and in some cases a transmembrane γ subunit. Ten α₁ subunits, four α₂δ complexes, four β subunits, and two γ subunits are known. The Ca_v1 family of α₁ subunits conduct L-type Ca²⁺ currents, which initiate muscle contraction, endocrine secretion, and gene transcription, and are regulated primarily by second messenger-activated protein phosphorylation pathways. The Ca_v2 family of α₁ subunits conduct N-type, P/Q-type, and R-type Ca²⁺ currents, which initiate rapid synaptic transmission and are regulated primarily by direct interaction with G proteins and SNARE proteins and secondarily by protein phosphorylation. The Ca_v3 family of α₁ subunits conduct T-type Ca²⁺ currents, which are activated and inactivated more rapidly and at more negative membrane potentials than other Ca²⁺ current types. The distinct structures and patterns of regulation of these three families of Ca²⁺ channels provide a flexible array of Ca²⁺ entry pathways in response to changes in membrane potential and a range of possibilities for regulation of Ca²⁺ entry by second messenger pathways and interacting proteins.