Atrial fibrillation (AF) is a growing clinical problem associated with increased morbidity and mortality. Although rhythm control strategies are preferable to those of rate control, pharmacologic therapy capable of widely applicable, safe, and effective AF suppression is not available. Recent studies have uncovered significant differences in the characteristics of atrial and ventricular sodium channels, leading to identification of drugs capable of atrial-selective inhibition of sodium channel current (I Na ). These agents are capable of atrial-selective depression of I Na -dependent parameters and thus effective and safe suppression of AF. This review describes this and other strategies under development for the pharmacologic management of AF.