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Bilirubin has traditionally been considered a cytotoxic waste product. However, recent studies have shown bilirubin to have anti-oxidant, anti-inflammatory, vasodilatory, anti-apoptotic and anti-proliferative functions. These properties potentially confer bilirubin a new role of protection especially in coronary artery disease (CAD), which is a low grade inflammatory process exacerbated by oxidative stress. In fact, recent literature reports an inverse relationship between serum concentration of bilirubin and the presence of CAD. In this article, we review the current literature exploring the association between levels of bilirubin and risk of CAD. We conclude that current evidence is inconclusive regarding the protective effect of bilirubin on CAD. A causal relationship between low serum bilirubin level and increased risk of CAD is not currently established.