The voltage-gated Na+, Ca*+, and K+ channels are responsible for the generation of action potentials in neurons and other excitable cells. These channels are also involved in cellular regulation in nonexcitablecell types. Voltage-gated ion channels all contain principal subunits (designated a or al) that are members of a common channel gene family and are responsible for the voltage-gated ion conductance which is the defining characteristic of these proteins (Numa, 1989; Catterall, 1988, 199l; Jan and Jan, 1989, 1992). However, in nearly every case studied to date, the principal subunits of the voltage-gated ion channels are expressed in cells as a specific protein complex with one or more auxiliary subunits, which strongly influence the activation, inactivation, or modulation of the principal subunits when coexpressed in heterologouscells. For example, the 8 subunits of Na+, Ca2+, and K+ channels accelerate the rate of inactivation of the channels, in one case by more than IOO-fold. The auxiliary subunits often confer critical physiological characteristics needed for normal function of the cells in which the ion channels are expressed. In some cases, the auxiliary subunits are functionally analogous to the regulatory subunits of allosteric enzymes and exert critical control of cellular excitability. This review focuseson the molecular properties and functional roles of these important ion channel components.