Atrial fibrillation is the most common clinically relevant arrhythmia and preferentially afflicts elderly persons, especially persons aged >/=75 years, with associated complications of ischemic stroke and other adverse outcomes. More than 2.2 million Americans currently have atrial fibrillation, and this number is expected to increase by at least 2.5-fold over the next 50 years. With the aging of the US and international populations, as well as the rising prevalence of clinical risk factors, the incidence and prevalence of atrial fibrillation are rising rapidly. While improved adherence to existing risk-based therapies can reduce thromboembolic complications in elderly persons, additional research is needed to determine novel approaches to prevent the initial development of atrial fibrillation in order to decrease the individual and public health burden of this condition.