Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice. Until recently, a rhythm control strategy for AF has been limited by drug toxicity and side-effects, and landmark AF trials have shown that such a strategy is not superior to a rate control one. New antiarrhythmic drugs, free of undesired effects, would enhance the rhythm control strategy, with the possibility of sinus rhythm restoration and maintenance. One of the promising drugs recently approved for clinical use is dronedarone. This drug has amiodarone-like antiarrhythmic and electrophysiological properties, despite it having a modified structure and lacking an iodine moiety. Thus, dronedarone lacks amiodarone's organ toxicity (including adverse thyroid and pulmonary effects). The efficacy of dronedarone has been investigated in several clinical trials, proving its effect in the prevention of AF recurrence, rate control in paroxysmal/persistent and permanent AF, reduction of cardiovascular hospitalization or death from any cause, and others. Indirect comparisons with amiodarone, as well as one head-to-head study of the two drugs, indicate that the relative safety of dronedarone may be at a cost of its lower antiarrhythmic efficacy compared with amiodarone.