Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in clinical practice and is associated with a higher risk of thromboembolic events. CHA2DS2VASc score enables identification of those patients with AF who will most benefit from anticoagulation therapy and low-risk patients with AF who do not need any antithrombotic therapy. Antithrombotic drugs especially oral anticoagulants (OACs) are the mainstay of therapy to prevent stroke in patients with AF. Although vitamin K antagonists (VKAs) were the only available drugs for decades, numerous non-vitamin K antagonist oral anticoagulants (NOACs) have been developed and marketed for stroke prevention in recent years. The risk of stroke was reported to decline up to 68 % with OAC therapy, associated with good anticoagulation control with VKAs, assessed by time in therapeutic range (TTR). In low TTR values, VKAs were found to be associated with severe complications, and a minimum TTR of 58 % should be achieved to expect a net benefit from being on OAC therapy. Narrow therapeutic index, drug-drug interactions, and the need for close monitoring are the main disadvantages of VKAs, and management of patients have dramatically improved after the introduction of NOACs. NOACs have a more predictable anticoagulant affect which allows a fixed-dose regimen. The efficacy and safety of NOACs have been shown not only in large randomized controlled clinical trials but also in observational studies. The main advantages of NOACS such as "fixed-dose regimen" and "no need for regular anticoagulant therapy monitoring" may also be the Achilles heel of the use of these agents. Fixed-dose regimen may not be appropriate for elderly, for patients with chronic kidney disease, and for patients using interacting drugs. Adherence to NOAC therapy is another concern as it may be as low as 50 % in the chronic use of cardiovascular drugs, especially if the drug has no apparent affect to the patient. Thus, appropriate use of OACs among non-valvular AF (NVAF) patients is essential for stroke prophylaxis. We intended to review the use of OAC therapy among (NVAF) patients.