Atrial fibrillation is a prominent cause of morbidity and mortality in developed countries. Current treatment strategies center on controlling heart rate while allowing fibrillation to persist or targeting fibrillation primarily and attempting to maintain sinus rhythm. Pharmacological therapies are largely successful for rate control, although mild toxicities are common. Rhythm control strategies are often unsuccessful, leaving patients in atrial fibrillation despite attempts to maintain sinus rhythm. This review will discuss novel biological strategies that are currently under development and may eventually have impact on the management of atrial fibrillation.