Atrial fibrillation (AF) is the most common arrhythmia worldwide, characterized by uncoordinated atrial activation leading to a loss of effective atrial contraction and increased risk for atrial thrombi formation, promoting an increased risk of cardioembolic strokes and mortality, and associated increased healthcare expenditure. Therefore, stroke prevention represents a key focus in managing patients with atrial fibrillation, and strategies to achieve this aim have drastically evolved over the years. Previously, aspirin and warfarin were the cornerstone of stroke prophylaxis. However, direct oral anticoagulants have emerged and are now recognized as a safer and more effective alternative for non-valvular AF. Meanwhile, newer non-pharmacological methods to prevent AF related strokes, such as left atrial appendage occlusion devices, have been approved to ameliorate the need for lifelong anticoagulation in patients with elevated bleeding risks. This review outlines the current recommendations and provides an overview of the literature on stroke prevention in patients with atrial fibrillation, particularly focusing on using direct-acting oral anticoagulants. Comparisons between these agents and special considerations for use are also reviewed.