Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is associated with a five-fold increase in the risk for ischemic stroke. Therefore, lifelong use of anticoagulants is crucial to reduce the morbidity and mortality burden of AF. The incidence of AF in chronic kidney disease (CKD) is two to three times greater than in the general population, and there is a mutual aggravation of the two conditions as well as the presence of both an increased thromboembolic risk in CKD and an increased bleeding risk in severe CKD. The preservation of kidney function in patients with cardiovascular diseases is important, as the latter is the leading cause of death in patients with eGFR <60 mL/min/1.73 m2. Similarly, kidney dysfunction is a serious limitation to the use of many cardiovascular drugs, including anticoagulants. Evidence is present for the faster progression of kidney disease with vitamin K antagonists, likely due to the vitamin K-related process of vascular calcification. Conversely, direct oral anticoagulants (DOACs) have been shown to reduce the progression of CKD and have a beneficial effect as far as the modulation of inflammation and oxidative stress are concerned in experimental models. Another less-discussed problem is the use of DOACs in advanced CKD.