Genome-wide association studies for coronary artery disease utilizing the case control association study approach has identified 50 genetic risk variants associated with coronary artery disease or myocardial infarction. All of these genetic variants are of genome wide significance and replicated in an independent population. It is of note that 35 of these 50 genetic risk variants act through mechanisms as yet unknown. These findings have great implications for the pathogenesis of atherosclerosis, as well as new targets for the development of novel therapies for the prevention and treatment of CAD. The genetic variant PCSK9 has already led to the development of a monoclonal anti-body which is undergoing assessment in phases I, II, and III clinical trials. This therapy shows very promising results and since it increases removal of LDL-C, it is complementary to current statin therapy. Assessing the beneficial or deleterious effects of a lifelong exposure to a genetic risk variant (Mendelian randomization) will be an important adjunct to clinical trials.