Over the last 25 years, considerable effort has been expended to develop strategies for prevention of sudden death with antiarrhythmic drugs. However, in large-scale clinical trials, antiarrhythmic drugs have either an adverse or, at best, neutral effect on all-cause mortality. Recent trials have clearly shown the superiority of implantable cardioverter-defibrillators in patients at high risk of arrhythmic death. In contrast, drugs that prevent the development or progression of coronary heart disease, including statins, antiplatelet drugs, thrombolytic agents, ß-adrenoceptor antagonists, angiotensin-converting enzyme inhibitors, and aldosterone antagonists, reduce both sudden death and all-cause mortality. Drug therapy has a bright future in the prevention of sudden death, but it lies with drugs altering the progression of underlying heart disease rather than with blockade of specific ion channels...