© Springer International Publishing AG 2018. Over the last century uric acid has been considered a possible risk factor for hypertension, cardiovascular disease, and kidney disease. Only in the last 15 years, however, have there been animal models and clinical trials to support a truly mechanistic link. Results from animal models suggest a two-phase mechanism for the development of hyperuricemic hypertension, in which uric acid induces acute vasoconstriction by activation of the renin-angiotensin system, followed by enhanced uric acid uptake into vascular smooth muscle cells leading to cellular proliferation and secondary arteriolosclerosis that impairs pressure natriuresis. The acute phase of hypertension in that model remains uric acid dependent and sodium independent, whereas the chronic hypertension in experimental models becomes uric acid independent and sodium dependent. Small clinical trials, performed in adolescents with newly diagnosed essential hypertension, demonstrate that reduction of plasma uric acid can reduce blood pressure. Small clinical trials in older adults and persons with chronic renal disease have demonstrated less response to urate lowering therapy, consistent with the two-step model. The available data suggest that uric acid, given its apparent role in the pathogenesis of hypertension, may be a viable target for treatment or prevention in some cases of early onset hypertension.