Ca2+ channel antagonist drugs inhibit voltage-gated Ca2+ channels in many different cell types. Inhibition of Ca2+ channels in smooth muscle and cardiac muscle cells by these drugs is valuable in the therapy of a wide range of cardiovascular disorders including hypertension, atrial arrhythmia and angina pectoris. Additional uses under evaluation are protection against ischemic damage during myocardial infarction and stroke and in a wide range of other conditions. Further understanding of the sites and mechanisms of action of Ca2+ channel antagonists, as described in this review by Bill Catterall and Jörg Striessnig, will provide new insight into the design of novel therapeutic agents acting on Ca2+ channels and provide further understanding of Ca2+ channel structure and function.