Cellular respiration in an oxygen-rich environment leads to the generation of reactive oxygen species. These partially reduced forms of molecular oxygen can readily react with biological molecules, often modifying their normal biological function. Antioxidant enzyme mechanisms have evolved to eliminate reactive oxygen species and minimize the oxidant stress caused by their reactivity. Inherited and acquired deficiencies of key antioxidant enzymes lead to a dysregulated redox environment, which can promote pathobiology; when this redox dysfunction occurs in the blood vessel, vascular disease ensues. In this article, we consider three distinct antioxidant enzyme deficiencies - glucose-6-phosphate dehydrogenase, glutathione peroxidase-1 and glutathione peroxidase-3 - and their consequences for vascular disease.