OPINION STATEMENT: Hypertension is a global public health problem affecting one-fourth of the world's population. A subset of these patients with resistant hypertension presents a particular management problem and suffers a marked increase in cardiovascular risk. Treatment options have been limited, but the past decade has witnessed the emergence of catheter-based renal denervation to interrupt the sympathetic nervous system, long considered to play an important role in the development and maintenance of hypertension. Phase 1 and 2 studies reported remarkable reductions in blood pressure and sparked an excessive exuberance that ground to a halt with negative results of the SYMPLICITY HTN-3 pivotal trial. The subsequent and sober reappraisal has shed light on potential failure modes. Armed with appropriately cautious optimism, the field has resumed its move forward to realize the potential for therapeutic application in hypertension and other conditions characterized by sympathetic overactivity. This article summarizes the rich experimental data, early surgical experience, and available clinical trial results for catheter platforms. It concludes with discussion of knowledge gaps, lessons learned, and future directions.