In patients diagnosed with chronic kidney disease (CKD), atrial fibrillation (AF) is associated with an increased risk of thromboembolism and stroke. Moreover, patients with CKD-especially those in end-stage renal disease-also present an increased risk of bleeding. Oral anticoagulation is the most effective form of thromboprophylaxis in patients with AF and an increased risk of stroke. However, the underuse of these drugs was observed, mainly due to safety reasons and restricted evidence on efficacy. Much evidence suggests that non-vitamin K-dependent oral anticoagulant agents significantly reduce the risk of stroke, intracranial hemorrhage, and mortality, with lower to similar major bleeding rates compared with vitamin K antagonists, such as warfarin, in normal renal function subjects. Thus, they are currently recommended for that group of patients. However, their metabolism is largely dependent on the kidneys for elimination, and current knowledge in this area is limited due to patients with a decreased glomerular filtration rate are usually excluded from clinical trials. The present review article focuses on currently available data on oral anticoagulants in patients with moderate to advanced chronic kidney disease and those with end stage renal disease.