Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide, and it is associated with an elevated risk of thromboembolic events, including ischemic stroke. Evidence suggests that at least 90 % of left atrial thrombi discovered in patients with AF are localized to the left atrial appendage (LAA). Surgical ligation or excision of the LAA is considered the standard of care in patients who undergo mitral valve surgery or as an adjunct to a surgical Maze procedure for treatment of AF. In addition, in selected patients with AF and an elevated risk of thromboembolic events, particularly in those with contraindication to oral anticoagulation (OAC) therapy, it is reasonable to consider LAA exclusion to offer protection against ischemic stroke and other embolic complications. This can be achieved through a number of different strategies, including surgical amputation or ligation of the LAA, percutaneous endocardial occlusion of the LAA by deployment of occlusive devices, and also ligation of the LAA via a closed-chest, percutaneous, epicardial catheter-based approach in select patients. Although results from several recent percutaneous LAA closure and ligation studies are highly promising, the evidence for long-term efficacy and safety is insufficient to presently recommend this approach to all patients other than those in whom long-term OAC is contraindicated. Future randomized studies are required to further address the long-term safety and efficacy of these therapeutic options. Finally, the role for LAA occlusion and ligation seems less clear in patients who undergo successful catheter ablation of AF, since at least in a subgroup of these patients antiplatelet therapy alone has been shown to be sufficient.