Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with an increased risk of thromboembolic complications and stroke. Therefore, the implementation of thromboembolic preventive treatment is the cornerstone of quality management in AF patients. During the last 60 years, vitamin K antagonists remain at the forefront of antithrombotic management of AF patients. Randomized trials have demonstrated their superiority over aspirin as well as over the combination of aspirin and clopidogrel with similar safety profile. However, the disseminated use of vitamin K antagonists among suitable candidates is hampered by their inherent limitations. As a result, a considerable proportion of AF patients do not receive this life-saving therapy. In the last few years, novel anticoagulants targeting factors IIa (dabigatran) and Xa (rivaroxaban, apixaban, edoxaban) in the coagulation cascade have been developed. Recently completed phase III mega-trials of dabigatran, rivaroxaban and apixaban have provided cumulative evidence in favor of these novel anticoagulants. Their main advantages, apart from their treatment efficacy, include the reduced rate of intracranial hemorrhage, the lack of need for routine coagulation monitoring, the predictable anticoagulation response and the limited interaction with food and drugs. In the present manuscript we present a critical appraisal of the recent trials focusing on issues that are expected to influence decision making on selection of novel anticoagulants.