The risk for stroke, precipitated by venous thromboembolism, is increased five-fold in people who have atrial fibrillation (Why Atrial Fibrillation, 2014). Oral anticoagulation treatment has been shown to be effective in the prevention and reduction of atrial fibrillation-related thromboembolic events. Warfarin (Coumadin, Jantoven), the most widely-used oral anticoagulant, was first approved for human use in 1954 (Pirmohamed, 2006). Since then, it has a long track record of treating patients in need of oral anticoagulation therapy. However, the recent introduction of novel non-vitamin K oral anticoagulants (NOACs,) also known as direct oral anticoagulants, such as rivaroxaban (Xarelto), apixaban (Eliquis), and dabigatran (Pradaxa) have made them popular alternatives to Warfarin. A disadvantage with most NOACs is that they are considered to be non-reversal drugs. There is currently no antidote to counteract the effects of overdosing on some of the medications. Also, the cost of these drugs to consumers may be prohibitive compared to the price of warfarin. This article will discuss the indications, benefits, complications, and controversies surrounding the increasing use of these relatively new medications to help prevent both stroke and venous thromboembolism, as well as manage the deleterious consequences of atrial fibrillation.