Voltage-sensitive Ca2+ channels are a large family of related heterooligomers that couple cell excitability to intracellular signalling. Recent studies on mice carrying Ca2+ channel mutations, or in which Ca2+ channel subunits have been deleted, have provided important information about the roles carried out by these molecules in cardiovascular function, pain, epilepsy, migraine and deafness, in addition to further defining how Ca2+ channels regulate the physiology of excitable cells.