The activities of multiple oxidases, including Nox oxidases, nitric oxide synthase (NOS), xanthine oxidase, cytochrome P450, cyclooxygenase, and mitochondria can contribute to the generation of oxidant species in the vessel wall. Each of these systems has specific mechanisms controlling oxidase activity and roles in physiologic or pathophysiologic regulation. The NAD(P)H cellular redox systems have major roles in controlling oxidase activities, the metabolism of oxidant species, and signaling systems regulated by these species. The Nox oxidases have unique roles in oxidant signaling because they are a basal source of superoxide production in vascular cells, which are subject to regulation by receptor activation, stimuli such as stretch, and metabolic stress such as hypoxia.