Four non-vitamin K antagonist oral anticoagulants (NOACs) are approved for use to reduce the risk of stroke and systemic embolism in patients with atrial fibrillation (AF). However, data are limited regarding the use of NOACs in the obese population. This manuscript summarizes current concepts regarding obesity in patients with AF and reviews in depth the data on the efficacy and safety of NOACs in obese patients with AF. The Pubmed database was searched for relevant articles. When evaluating obese patients with AF, weight loss is important to reduce disease burden. Recent analyses of the four NOAC versus warfarin trials (RE-LY, ROCKET-AF, ARISTOTLE, and ENGAGE AF-TIMI 48) stratified by body mass index (BMI) demonstrate preserved efficacy with NOACs versus warfarin in obese patients, with similar risk of major bleeding. Although the data are limited in class III obese patients (body mass index ≥40kg/m2), the efficacy and safety of apixaban or edoxaban appears to be similar to warfarin in patients with BMI 40-50kg/m2. In conclusion, these new data should be considered in updated guidelines, which currently provide limited, and sometimes conflicting recommendations regarding the use of NOACs in obese patients, particularly in severely obese patients.