Arterial thromboembolism is a sudden obstruction of arterial blood flow caused by dislodgment of a blood clot from the site of its formation. Atrial fibrillation (AF) is the most common cardiac arrhythmia and a major risk factor for arterial thromboembolism in clinical practice. Most of AF-related arterial thromboembolic events affect the cerebral circulation, leading to increased mortality or long-term disability from stroke. In the setting of AF, stroke is more likely to be fatal or associated with longer hospitalization, greater disability and higher rates of recurrence. Anticoagulant therapy reduces the risk of stroke, and the greatest benefit is achieved in patients at highest absolute risk. Aspirin is a less effective option, and should not be considered as an equivalent alternative for AF patients with a moderate stroke risk, who are eligible for oral anticoagulation. Nonetheless, anticoagulant therapy remains underused in AF patients with high stroke risk, particularly in the elderly, whilst it might perhaps be overused in the low risk patients. This could also be related to limitations in current risk stratification schemas for stroke and bleeding complications of anticoagulant therapy in AF patients in contemporary clinical practice. In this review article, we present an overview of current therapeutic strategies, new developments and future perspectives for the prevention of arterial thromboembolism in the context of AF and thromboembolism. We also discuss risk factors for stroke and bleeding complications, current risk stratification issues and emerging strategies for more accurate identification of AF patients who should be anticoagulated.