Resistant hypertension is a vexing medical problem. It is defined as poorly controlled blood pressure in spite of treatment with optimal doses of ≥3 different classes of drugs.1 In this context, the archetypical patient with resistant hyper-tension is an obese person in late middle age who might or might not have coexisting diseases, such as diabetes mellitus, peripheral vascular disease, and mildly impaired ventricular function or diastolic dysfunction. A blood pressure value of 150 to 160/95 mm Hg or greater would not be uncommon, and such a value puts these individuals at markedly increased risk for heart attack and stroke. So, the question is what to do about these difficult-to-treat patients? Although many of these patients might respond to truly intensive multimodal lifestyle modification, this has been difficult to implement in a widespread way in real popu-lations.2 Our obesogenic modern world is also a blood pres-sure raising one. In this context, device therapy, most notably catheter-based renal denervation (also called renal nerve abla-tion), has moved to fill this therapeutic breach.3 How Does Renal Denervation Work? There are 2 basic theories about how renal denervation might lower arterial pressure. First, a reduction in sympa-thetic activity to the kidney will limit activation of the renin-angiotensin-aldosterone system and blunt the vicious blood pressure–raising cycle seen when this system is activated. A second idea is that in at least some patients with resistant hypertension inflammation or some other stimulus is activat-ing blood pressure–raising renal afferents, which in turn evoke increases in sympathetic activity. There is at least some evi-dence in support of both concepts, and emerging ideas have stressed the role of sympathoexcitatory renal afferents in hypertension.