PURPOSE OF REVIEW: Review the renal nerve anatomy and physiology basics and explore the concept of global vs. selective renal denervation (RDN) to uncover some of the fundamental limitations of non-targeted renal nerve ablation and the potential superiority of selective RDN. RECENT FINDINGS: Recent trials testing the efficacy of RDN showed mixed results. Initial investigations targeted global RDN as a therapeutic goal. The repeat observation of heterogeneous response to RDN including non-responders with lack of a BP reduction, or even more unsettling, BP elevations after RDN has raised concern for the detrimental effects of unselective global RDN. Subsequent studies have suggested the presence of a heterogeneous fiber population and the potential utility of renal nerve stimulation to identify sympatho-stimulatory fibers or "hot spots." The recognition that RDN can produce heterogeneous afferent sympathetic effects both change therapeutic goals and revitalize the potential of therapeutic RDN to provide significant clinical benefits. Renal nerve stimulation has emerged as potential tool to identify sympatho-stimulatory fibers, avoid sympatho-inhibitory fibers, and thus guide selective RDN.