In past decades, numerous experimental and clinical studies have improved our knowledge of the electrophysiological effects of sodium channel blockers, as well as of the mechanisms of arrhythmogenesis. However, the mechanisms of antiarrhythmic as well as potentially proarrhythmic drug action have been less well clarified. Sodium channel blocker agents have different effects on the normal, ischaemic, and failing heart since their antiarrhythmic actions depend on the substrate and the mechanisms of arrhythmogenesis, as well as other mostly interrelated cardiac and non-cardiac factors. Strict criteria of efficacy and safety have to be applied when sodium channel blockers are used for the treatment of ventricular arrhythmias.