Despite remarkable advances in identifying and managing coronary heart disease, the global burden of cardiovascular (CV) risk and levels of undetected, subclinical heart disease remain enormous. Substantial numbers of patients do not reach their therapeutic goals, others are unable to tolerate the treatments, half may fail to adhere to their programs, and in those who do attain their targets, major cardiovascular events may continue. Wellknown risk factors, such as obesity and diabetes, have now gained the upper hand, with no evidence-based remedy capable of reversing this trend. All told, less than 1% of American adults and adolescents qualify for ideal CV health; world-wide, the growing prevalence of CV risk factors in children is imposing. A number of novel emerging drug therapies are in development, some recently approved for use in patients with familial hypercholesterolemia.Hopefully, they will contribute significantly to the current therapeutic armamentarium. However, for meaningful improvement in total and residual CV risk, an optimal mix of all available modalities will likely be necessary, including earlier and more effective prevention, aggressive medical care, revascularization and device implantation, judicious use of novel agents, and reengineering of the environment.