Although an approximate 13 million individuals in the United States are known to have coronary artery disease (CAD), only a small percentage of them develop unstable CAD each year. About 500,000 to 1 million people present annually with an ST-elevation myocardial infarction (STEMI), some of whom had never been diagnosed with CAD. The known etiology of coronary occlusion is the disruption of the atherosclerotic plaque within the vascular wall, and vascular inflammation is thought to lead to this disruption. Since many patients with CAD never suffer an myocardial infarction, the question then becomes why does inflammation-induced plaque disruption occur in only some patients? The explanation may lie in differing genetic and phenotypic characteristics. A greater understanding of the pathophysiology and the identification of new genetic and inflammatory markers are slowly leading to new therapeutic interventions that promise to greatly reduce the morbidity and mortality associated with CAD within the foreseeable future.