Human exposure to environmental toxicants is known to contribute to the development of vascular disease. Inhalation of environmental toxicants induces inflammation and oxidative stress in the vascular system and results in tissue damage, with subsequent impairment of the vascular system. The induction of antioxidant enzyme expression is one of the most crucial components of the cellular defense against environmental insults, and represents an adaptive response. The antioxidant enzyme-mediated adaptive response has been demonstrated to attenuate toxicity caused by oxidative stress as well as inflammation. Accumulating evidence indicates that antioxidant enzymes may protect against environmental toxicants. This review highlights the role of antioxidant enzymes in the adaptive response to environmental toxicants, and explores strategies for their clinical use.