The left atrial appendage (LAA) is the primary nonvalvular cause of cardioembolic stroke in patients with atrial fibrillation (AF). Warfarin and direct thrombin inhibitors such as dabigatran are presumed to prevent formation of LAA thrombus, and are first-line treatments to prevent ischemic stroke in AF. However, these medications carry many contraindications such as hemorrhage, and can interact with many drugs and supplements. Epicardial and endovascular techniques for occlusion of LAA are being explored, whether to mitigate the need for anticoagulation in patients at risk of bleeding or as a first-line therapy to reduce the risk of thromboembolic stroke. The purposes of this article are to 1) review the LAA structure and its potential contribution to ischemic stroke; 2) discuss the results of surgical and endovascular trials of LAA occlusion on risk of stroke and adverse events in AF patients; and 3) present early data on devices in development.