The study of vascular biology has provided strong evidence for the role that free radical attack plays in the pathogenesis of cardiovascular diseases. The endothelial cell (EC) dysfunction that results from exposure to oxidative stresses, such as oxidized LDL, influences vascular cell gene expression, promoting smooth muscle cell (SMC) mitogenesis and apoptosis. These factors also play an important role in atherogenesis, which is attenuated by antioxidants. Thus, antioxidants are important to understanding the pathophysiology of cardiovascular diseases and to constructing an effective treatment strategy for these patients. Over the last decade, there has been a tremendous interest in the biology of heme oxygenase-1 (HO-1), which exhibits antioxidant effects in various forms of tissue injury. Moreover, the reaction is also the major source of carbon dioxide (CO) in the body, which is a physiologically important gaseous vasodilator that inhibits SMC proliferation. Thus, HO-1-derived products provide various mechanisms to maintain cardiovascular homeostasis. We review recent work on the cellular and molecular biological aspects of the HO/CO system in vascular pathophysiology.