Prevention of stroke and systemic thromboembolism remains the cornerstone for management of atrial fibrillation (AF) and flutter. Multiple risk assessment models for stroke and systemic thromboembolism are currently available. The score, with its known limitations, remains as the recommended risk stratification tool in most major guidelines. Once at-risk patients are identified, vitamin K antagonists (VKAs) and, more recently, direct oral anticoagulants (DOACs) are the primary medical therapy for stroke prevention. In those with contraindication for long-term anticoagulation, left atrial appendage occluding devices are developing as a possible alternative therapy. Some controversy exists regarding anticoagulation management for cardioversion of acute AF (<48 hours); however, systemic anticoagulation precardioversion and postcardioversion is recommended for those with longer duration of AF. Anticoagulation management peri-AF ablation is also evolving. Uninterrupted VKA and DOAC therapy has been shown to reduce perioperative thromboembolic risk with no significant escalation in major bleeding. Currently, under investigation is a minimally interrupted approach to anticoagulation with DOACs periablation. Questions remain, especially regarding the delivery of anticoagulation care and integration of wearable rhythm monitors in AF management.