Stroke is the most feared complication of atrial fibrillation (AF).  Targeting the left atrial appendage (LAA) mechanically is attractive as a means to simultaneously reduce stroke risk, the need for anticoagulation, and hemorrhagic complications in patients with non-valvular AF.  The results of the PROTECT-AF and PREVAIL randomized clinical trials support this approach as a viable therapeutic alternative to warfarin in selected patients and add to accumulating evidence regarding the importance of the LAA in thromboembolism in AF.  A number of devices for percutaneous LAA closure are under investigation or development.  In this article, key design features of these ligation and exclusion technologies will be discussed, with a focus on aspects of LAA morphology, relational anatomy, thrombosis, and thromboembolism relevant for successful device development and deployment.