Atrial fibrillation (AF) is the most frequent arrhythmia in common clinical practice and its prevalence is markedly increased among patients with chronic kidney disease (CKD). The presence of CKD increases the incidence of AF and vice versa. Both AF and CKD increase the risk of stroke or systemic thromboembolism and oral anticoagulation is the mainstay for thromboembolic event prevention in patients with AF. Novel oral anticoagulants (NOACs) are nowadays often used in patients with AF and CKD, but they display a variable degree of renal elimination and the risk of accumulation and bleeding increases among patients with CKD in particular as kidney disease progresses. While recent data have demonstrated that patients with Stage 3 CKD benefit even more from oral anticoagulation therapies in comparison with patients with normal renal function, relatively little is known about the best choice of anticoagulation in patients with advanced and, in particular, end-stage renal disease, as these patients were excluded from all pivotal Phase 3 NOACs trials. This review summarizes current knowledge on the efficacy and safety of these agents in individuals with CKD and provides CKD stage-specific recommendations.