© Springer Science+Business Media New York 2013. Over the last century, uric acid has been considered a possible risk factor for hypertension and cardiovascular disease. However, only in the last decade have animal models and clinical trials supported 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 the activation of renin-angiotensin-aldosterone system, followed by enhanced uric acid uptake into vascular smooth muscle cells leading to cellular proliferation and secondary arteriolosclerosis that impairs pressure natriuresis. This acute hypertension 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 serum uric acid can reduce blood pressure. While more research is clearly necessary, the available data suggest that uric acid may be causative in some cases of early onset hypertension.