Chronic kidney disease (CKD) is associated with substantial cardiovascular morbidity, including myocardial infarction, heart failure and stroke. Similar to CKD, atrial fibrillation (AF) is a prevalent arrhythmia that increases risk for both stroke and overall mortality. Recent studies demonstrate that both prevalence and incidence of AF is higher in patient with versus without renal impairment and risk for developing AF increases as renal function worsens. Potential mechanisms for the higher burden of AF in CKD patients include but are not limited to augmented sympathetic tone, activation of the renin-angiotensin-aldosterone system and myocardial remodeling. Similar to the general population, AF confers an increased risk for both stroke and overall mortality in the CKD population. The safety and efficacy of antithrombotic therapy across the spectrum of CKD remains unknown, however, as patients with advanced renal failure are frequently excluded from randomized trials. While treatment with vitamin K antagonists appears to reduce ischemic complications without significant bleeding harm in patients with mild to moderate CKD and AF, the risk benefit ratio of anticoagulation among thosewith advanced renal failure on dialysis requires further investigation. Prospective, randomized trials are war ranted to define the impact of antithrombotic therapy on reducing stroke risk in patients with both AF and CKD.