The prevalence of atrial fibrillation (AF) continues to increase worldwide. It is projected that by 2050, between 5 and 15 million Americans will have AF. Such predictions necessitate new advances in drug therapy. AF is associated with changes in ionic currents. Atrial fibrosis, changes in gap junctions and cell membranes act in concert to initiate and maintain AF. Significant advances in understanding the pathophysiology of this condition have led to numerous new drug discoveries in the last decade. We discuss newly patented molecules that act as sodium and potassium channel blockers, gap junction and intracellular calcium modulators, stretch receptor antagonists, ischemic ion current inhibitors and adenosine receptor agonists.