Overproduction of oxygen free radicals, which is mainly mediated by superoxide, occurs in human hypertension and a wide variety of animal models. There are several important enzymatic sources of superoxide production, including NADPH oxidase, xanthine oxidase and uncoupled nitric oxide synthase. Superoxide levels are also controlled through endogenous antioxidant systems and superoxide dismutase is the primary antioxidant in the vascular system. Strategies have therefore focused on combating hypertension and vascular disease through the inhibition of superoxide-generating enzymes, and scavenging superoxide. While results from animal studies are promising, no consensus has been reached on identifying a drug target for the reliable and effective treatment ofoxidative stress in hypertension.