Compared to patients with normal renal function, the prevalence of atrial fibrillation (AF) in chronic kidney disease (CKD) is increased, as is consequently the stroke prevalence in these patients. This increased risk of stroke in patients with CKD is caused not only by the increased prevalence of AF, but also by associated co-morbidities, and inherent platelet and vascular dysfunction. Paradoxically, imbalance in the same factors also increases the bleeding risk, imposing a dilemma as to whether anticoagulation should be prescribed or deferred, particularly in patients with end-stage renal disease (ESRD), in whom the bleeding diathesis and thromboembolic predisposition are most recalcitrant. Unfortunately, it is in this vulnerable population, in whom therapeutic options are most limited, that evidence-based studies relating to stroke prophylaxis are scarce, discordant and based only on registry observations. Pending randomized controlled studies on this issue, we will review important epidemiologic data and major recent registry-based studies that the clinician has to weigh when making the best decision on the issue of the prophylactic use of warfarin in patients with CKD with AF, focusing on patients with end-stage renal disease.