During the past 10 years there has been a major shift in antiarrhythmic drug development from class I to class III antiarrhythmic agents. The first two class III antiarrhythmic drugs that became available, sotalol and amiodarone, also have potent antiadrenergic actions. Newer antiarrhythmic drugs either block a specific ionic current (eg,dofetilide-induced blockade of the rapidly activating component of the delayed rectifier potassium current) or block multiple ionic channels (eg,ibutilide and azimilide) in order to prolong atrial and ventricular action potentials without other specific pharmacologic effects. Recent data suggest that these new class III antiarrhythmic drugs are highly effective for treating patients with rhythm disorders with an acceptable degree of proarrhythmia. This manuscript reviews the newer class III agents’ effectiveness in treating atrial and ventricular arrhythmias and the recent studies examining drug-induced prolongation of atrial repolarization to prevent or terminate postoperative atrial fibrillation.