Superoxide (O2-) is a key risk factor for cardiovascular disease (CVD), including atherogenesis, reperfusion injury, angina, restenosis following balloon angioplasty, and vein graft failure. Axiomatically, O2- reacts with nitric oxide (NO) to form peroxynitrite (ONOO) resulting in a depletion of endogenous vascular NO, which is now firmly associated with CVD. Furthermore, risk factors for CVD, in particular diabetes mellitus (DM), dyslipidemia, and hyperhomocysteinemia are all associated with oxidative stress OS. Antioxidant therapies, including the gene transfer of antioxidant enzymes, are potentially valuable in the treatment of CVD.