This issue of Interventional Cardiology Clinics examines approaches to left atrial appendage exclusion. Topics include stroke and bleeding risks in patients with atrial fibrillation, embryology and anatomy, rationale, catheter-based endocardial closure, pericardial access, catheter-based epicardial closure, surgical closure, device and left atrial appendage specific characteristic for successful closure, clinical results, the role of CTA and MRA imaging, imaging with TEE, post-procedural management, and prevention and management of complications.