Background- Worldwide, atrial fibrillation is the most common arrhythmia, and its symptoms and sequelae cause an enormous burden to patients and health systems. Stroke is associated with the greatest mortality and morbidity in patients with atrial fibrillation (AF). The last decade has seen great advances in scientific and therapeutic approaches to AF. Purpose- This review considers recent changes to stroke prevention, particularly focusing on new anticoagulants, antiarrhythmic drugs, and devices as well as future research directions. Summary of Review- A semi-systematic literature review was performed using search terms "atrial fibrillation" and "novel therapy" within the PubMed database from 2005 to 2011. The area of greatest progress has been novel anticoagulants with direct thrombin inhibitors and factor Xa inhibitors. Dabigatran is the only novel agent currently licensed for use in AF patients, but with several trials of novel agents pending and favorable results so far, other agents are likely to follow. Novel antiarrhythmic drugs, left atrial appendage occlusion, and upstream therapies all represent potential new approaches but require further research. CONCLUSIONS: Novel anticoagulant and arrhythmic agents are changing treatment guidelines and choices available to both patients and clinicians for stroke prevention in AF, but bring new considerations and long-term data are required, because most patients will require lifelong therapy. Future research must incorporate patient values and preferences, because novel therapies can potentially give very different treatment options, which must be explained for patients to make informed choices.