Atrial fibrillation and heart failure are growing epidemics in the developed world and often coexist. From clinical trials, warfarin is highly effective in reducing stroke in patients with atrial fibrillation. Equally important is the fact that in spite of well-designed trials, translation of the results of the data from the trials into clinical practice has been less than optimal. One of the reasons is that warfarin is a difficult drug to use. Thus there has been a concerted effort to develop an alternative to warfarin. Ximelagatran and Dabigatran, both direct thrombin inhibitors, are the furthest along in clinical development. Ximelagatran, while highly effective as an anticoagulant and safe with regard to bleeding, has been associated with liver function abnormalities; the importance of which needs resolution. Dabigatran is much earlier in development and is currently of unproven value. It is highly likely that alternatives to warfarin for stroke prevention will be available in the future and will likely result in a higher utilization rate of anticoagulants in patients with atrial fibrillation.