Stroke prevention is the primary goal in atrial fibrillation (AF) given its clinical and socioeconomic impact. With AF, the prevalence of thromboembolic stroke continues to rise and there is an urgent need to develop better strategies of stroke prevention. Warfarin, although effective when used appropriately, is burdened by underutilization, narrow therapeutic windows, and life-threatening bleeding complications. Novel pharmacologic agents have been plagued by off-target toxicity and only modest improvement in bleeding complications over warfarin. Because most thromboemboli arise from the left atrial appendage (LAA), surgical exclusion of the LAA is often used in AF patients undergoing cardiac surgery. Percutaneous device LAA closure has now been developed as an adjunct and as an alternative to pharmacotherapy in patients with AF. Promising randomized data are available with the WATCHMAN device, while several other devices are in various stages of clinical and preclinical development.