Recent studies in clinical and experimental obesity suggest that the hypertension enmeshed within the metabolic syndrome is neurogenic, ie, initiated and sustained by activation of the sympathetic nervous outflow to the kidneys. Whether the stimulus for this is hyperinsulinemia, leptin excess, or perhaps coexistent obstructive sleep apnea remains problematic. Weight reduction and an aerobic exercise program remain pivotal in normalizing obesity-related hypertension. If these fail, the ideal antihypertensive drug should target the underlying neural pathophysiology of the hypertension, but should not contribute to weight gain by inhibition of thermogenesis or worsen the existing insulin resistance. Centrally acting sympathetic nervous inhibitors of the imidazoline-receptor binding class appear to meet these prerequisites, though no definitive empirical evidence is yet available to establish them as the preferred drug class...