Atrial fibrillation represents a major clinical, social and economical matter, and its importance is expected to increase even more in the near future. The progressive ageing of population is associated with an inevitable rising in incidence and prevalence of this rhythm disorder, which limits functional capability, favours occurrence of cerebrovascular events and increases peoples request for emergency room visits and hospital recovery. In spite of the increasing successes of the interventional non-pharmacological therapies, drug treatment of patients with atrial fibrillation in relation to conversion to sinus rhythm and prevention of recurrences, maintains a critical role. Several antiarrhythmic drugs are nowadays available, but their efficacy is limited by the high rate of arrhythmias recurrences and by side effects during acute and chronic treatment. Drugs interfering with potassium channels (Class III drugs) have been proposed and used in patients with atrial fibrillation. Aim of this review is to discuss the most recent data on the efficacy and feasibility of class III drugs in atrial fibrillation. Experimental and clinical data on dronedarone, ibutilide, dofetilide, azimilide, ersentilide and ambasilide will be hereby discussed.