Insulin resistance, dyslipidemia, hypertension, obesity, cardiovascular disease, and chronic kidney disease cluster together, and the incidence of all of these disease states is increasing throughout the world. Current strategies for hypertension management-including the use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium antagonists, and thiazide diuretics-are effective for most patients. However, as the incidence of hypertension increases in this target population, so does that of resistant hypertension. As such, significant research and effort must be put forth to bring blood pressure to goal and delay or prevent target organ damage. Such efforts should frequently include a dihydropyridine calcium channel blocker such as amlodipine. Other agents that are currently underused in this population for the treatment of resistant hypertension include nebivolol, carvedilol, aliskiren, and aldosterone antagonists. Finally, significant potential is seen for darusentan, an endothelin antagonist, if it comes to market.