Understanding the anatomy, physiology, and arrhythmogenic and thrombogenic roles of the left atrial appendage (LAA) has become very important. The potential deleterious effects of this chamber in patients with atrial fibrillation have led to the development of specific treatments for this structure. It has been established that the LAA is the area where the vast majority of thrombi in nonvalvular atrial fibrillation are formed and that some LAA morphologies may actually facilitate thrombi formation and risk stratification for thromboembolic events in patients with low CHA2DS2-VASc scores. Likewise, clinical data supporting the role of LAA electric isolation to improve freedom from all-atrial arrhythmias are rapidly growing. Acute LAA electric isolation can be achieved in most cases of catheter ablation for atrial fibrillation. However, late LAA reconnections are frequent. Special considerations should be taken when this procedure is performed to avoid myocardial perforation, left phrenic nerve, and left circumflex coronary artery damage. LAA electric isolation is a safe procedure that does not increase the risk of stroke as long as patients remain compliant with lifelong anticoagulation regardless of CHA2DS2-VASc score. Finally, ligation of the LAA has recently been associated with modulation of the renin-angiotensin-aldosterone system with clinical implications in blood pressure control.