Atrial fibrillation (AF) is associated with a significant burden of morbidity and increased risk of mortality. Beyond outstanding advances in catheter ablation procedures, antiarrhythmic drug therapy remains a corner-stone to restore and maintain sinus rhythm. However, potentially life-threatening hazards (proarrhythmia) and significant non-cardiac organ toxicity have made new drug development of prominent relevance. Multichannel blocking, atrial selectivity, and the reduction of the risk of adverse events have all constituted the main theme of modern antifibrillatory drug development. Dronedarone, an analog of amiodarone, has the unique characteristic of being the first antiarrhythmic drug demonstrated to reduce hospitalizations in AF. Dronedarone is associated with less systemic toxicity than amiodarone, although being less effective for sinus rhythm maintenance. Atrial selective agents have been developed to target ion channels expressed selectively in the atria. Among the most promising drugs of this class is vernakalant, which has been shown effective for the acute conversion of AF with small risk of proarrhythmia. Finally, increasing evidences support antiarrhythmic effectiveness of traditional non-antiarrhythmic drugs, such as renin-angiotensin system blockers, statins, and omega-3 fatty acids. In this article, we will focus on recent advances in antiarrhythmic therapy for AF, reviewing the possible clinical utility of novel antifibrillatory agents.