Despite improvements in cardiovascular outcomes, coronary artery disease (CAD) continues to be a major cause of death worldwide. South-Asians (SAs) show an increased risk of atherosclerosis and have the highest mortality rates from CAD than any other ethnic group. The greater susceptibility of SAs to CAD cannot be explained entirely by conventional risk factors alone. Other factors are involved, such as genetic predisposition and high prevalence of the metabolic syndrome and type-2 diabetes. CAD is more severe, extensive and malignant among SAs. It is often unsuspected and associated with adverse outcome requiring a more aggressive management strategy. With the growing SA population in North America, physicians need to be aware of the epidemiology, conventional causes, associated contributors, and adverse outcomes of CAD in this group. Importantly, physicians need a structured approach and an aggressive management algorithm for the optimal care of the high-risk SA patient population.