South Asians around the globe have the highest rates of coronary artery disease (CAD). These rates are 50% to 300% higher than other populations, with a higher risk at younger ages. These high rates of CAD are accompanied by low or similar rates of major traditional risk factors. The prevalence of diabetes is three to six times higher among South Asians than Europeans, Americans, and other Asians but does not explain the "South Asian Paradox." A genetic predisposition to CAD, mediated by high levels of lipoprotein(a), markedly magnifies the adverse effects of traditional risk factors related to lifestyle and best explains the South Asian Paradox. Although the major modifiable risk factors do not fully explain the excess burden of CAD, they are doubly important and remain the foundation of preventive and therapeutic strategies in this population. A more aggressive approach to preventive therapy, especially dyslipidemia, at an earlier age and at a lower threshold is clearly warranted.