Afferent renal sympathetic nerve signaling regulates central sympathetic outflow. In this regard, renal sympathetic denervation has emerged as a novel interventional strategy for treatment of patients with resistant hypertension. Despite the disappointing results of the Simplicity HTN-3 randomized controlled trial, promoters of renal denervation argue that the negative results were due to ineffective denervation technique and poor patient selection. Yet, long-term "pathologic" increase of efferent sympathetic nerve activity is observed in many chronic disease states characterized by sympathetic overactivity, such as arrhythmia, heart failure, insulin resistance, and chronic kidney disease. In this review, we highlight the contemporary evidence on the safety/efficacy of renal denervation in the treatment of patients with atrial fibrillation.