Failure to prescribe anticoagulation to prevent stroke in high-risk atrial fibrillation (AF) patients is a persistent and pervasive problem. Despite a multitude of evidence-based clinical practice guidelines, and five effective oral anticoagulants for stroke prevention, at least 30% of these patients remain unprotected. This talk will focus on understanding the root causes of the failure to prevent stroke crisis. The role of antithrombotic therapy, in particular direct oral anticoagulants, will be reviewed. Strategies for implementation of best practices for stoke prevention in AF will be highlighted.