Oxidative stress is believed to play a crucial role in the initiation and progression of atherosclerosis. In particular, oxidative stress could be involved in the pathogenesis of hypertension but, until now, there is still a debate whether oxidative stress is a cause or a result of hypertension. Nicotinamide adenine dinucleotide phosphate (NADPH) activation is considered as the major reactive oxygen species source and could be implicated in the pathogenesis of hypertension. A large body of evidences coming from animal studies have generally supported the hypothesis that high blood pressure is associated with increased oxidative stress and with NADPH activation; conversely, human studies provided divergent results. This review analyses the data reported so far to determine the role of NADPH oxidase in the pathogenesis of hypertension. © 2009 Adis Data Information BV. All rights reserved.