Atrial fibrillation (AF) is a major risk factor for disabling ischemic strokes. Anticoagulation is highly effective for stroke prevention in patients with AF, but a substantial number of patients are unable to sustain chronic therapy with warfarin. Most strokes in patients with AF are thought to arise from thrombus formation in the left atrial appendage (LAA); therefore, occlusion of the orifice of the LAA provides a theoretically appealing option for stroke prevention. Surgical exclusion of the LAA is increasingly performed in patients undergoing open-heart surgery, and thoracoscopic epicardial occlusion of the LAA has yielded promising early results. Percutaneous LAA occlusion devices have shown some success initial trials, but additional safety and efficacy data are required before this approach can be routinely considered. Here we discuss the LAA in relation to AF-related embolic stroke, and how LAA occlusion devices could be used in stroke prevention in patients who cannot tolerate chronic anticoagulant therapy.