Research over the years has shown that oxidative stress may be involved in the progression to coronary artery disease (CAD), suggesting a potential role for vitamin antioxidant therapy. Vitamin C was looked to as a potential treatment and epidemiological evidence seemed to indicate a protective cardiovascular effect. Data emerged from basic research that indicated that vitamin C positively regulated several components of the cardiovascular system, including restoration of antioxidant enzymes, improved arterial vasodilatation, reduction in inflammatory markers, and a better lipoprotein profile. Despite this initial optimism, subsequent analyses carried out in large clinical trials have shown that vitamin C supplementation has little therapeutic benefit. This paper reviews currently available evidence on the cardioprotective effect of vitamin C and the prospects for antioxidant treatment of CAD.