Serum uric acid may be an independent risk factor for cardiovascular disease. This review examines this association, potential mechanisms, and explores whether strategies to reduce uric acid will improve outcomes. The recent studies of xanthine oxidase inhibition are given particular focus. Epidemiological evidence supports the theory that uric acid is an independent risk factor for cardiovascular disease. Recent studies of losartan, atorvastatin and fenofibrate suggest that uric acid reduction contributes to the risk reduction offered by these therapies. Several small studies of xanthine oxidase inhibition have shown improvements in measures of cardiovascular function of a similar magnitude to that of other proven preventative treatments. These trial data and the convincing epidemiological evidence mandate that large clinical trials of uric acid-lowering strategies are performed in patients with or at high risk of cardiovascular disease. If such approaches are shown to be effective in reducing cardiovascular events, they would represent a novel and cost-effective preventative approach.