The Na+ channel is an important target for the action of antiarrhythmic drugs. Application of contemporary biophysical, biochemical and molecular biological techniques have added considerably to our knowledge of its structure, function, modulation and block by antiarrhythmic drugs. The increased mortality from the use of these drugs for prophylaxis of cardiac arrhythmias has forced a re-evaluation of their use and of the entire pharmacological strategy of arrhythmia management. Gus Grant and David Wendt review recent studies on the block and modulation of cardiac Na+ channels and the place of Na+ channel blockers in future antiarrhythmic drug development.