The treatment of atrial fibrillation (AF) takes a 2-pronged approach that addresses (1) symptoms caused by the arrhythmia and (2) safety, which is largely focused on reduction of the risk of stroke due to the effects of AF on blood flow. Treatment of AF includes rate-control and rhythm-control strategies. However, achieving control of AF symptoms will generally not protect a patient against the risk of stroke. Currently available antithrombotic agents effectively reduce the risk of stroke in patients with AF, and guidelines have been established for selecting the appropriate agent. Recommendations currently center on a choice between aspirin or warfarin (target international normalized ratio of 2.0-3.0) and are based on an assessment of the level of risk for the individual patient. The choice between aspirin or warfarin comes down to a choice between lower anticoagulant efficacy coupled with a lower bleeding risk versus higher anticoagulant efficacy coupled with a higher bleeding risk. Minimizing the risks of antithrombotic treatment in AF patients involves finding the appropriate balance between the risk for each individual of having a stroke while using less effective anticoagulation versus the risk of having a major bleeding event while using more effective anticoagulation.