Coronary artery disease (CAD) is the leading cause of death in the United States. Although CAD was formerly considered a lipid accumulation-mediated disease, it has now been clearly shown to involve an ongoing inflammatory response. Advances in basic science research have established the crucial role of inflammation in mediating all stages of CAD. Today, there is convincing evidence that multiple interrelated immune mechanisms interact with metabolic risk factors to initiate, promote, and ultimately activate lesions in the coronary arteries. This review aims to provide current evidence pertaining to the role of inflammation in the pathogenesis of CAD and discusses the impact of inflammatory markers and their modification on clinical outcomes.