Hypertension is a major contributor to the development of renal failure, cardiovascular disease, and stroke. These pathologies are associated with vascular functional and structural changes including endothelial dysfunction, altered contractility, and vascular remodeling. Central to these phenomena is oxidative stress. Factors that activate pro-oxidant enzymes, such as NADPH oxidase, remain poorly defined, but likely involve angiotensin II, mechanical stretch, and inflammatory cytokines. Reactive oxygen species influence vascular, renal, and cardiac function and structure by modulating cell growth, contraction/dilatation, and inflammatory responses via redox-dependent signaling pathways. Compelling data from molecular and cellular experiments, together with animal studies, implicate a role for oxidative stress in hypertension. However, the clinical evidence is still controversial. This review provides current insights on the mechanisms of the generation of reactive oxygen species and the vascular effects of oxidative stress and discusses the significance of oxidative damage in experimental and clinical hypertension.