The pharmacological approach to therapy of atrial fibrillation (AF) is often associated with adverse effects resulting in the development of ventricular arrhythmias. As a consequence, much of the focus in recent years has been on development of atrial-selective agents. Atrial-selective sodium channel blockers have recently been shown to exist and be useful in the management of AF. This review summarizes the available data relative to current therapies, focusing on our understanding of the actions of atrial selective sodium channel blockers in suppressing and preventing the induction of AF and electrophysiological properties that confer atrial-selectivity to these antifibrillatory drugs.