Genome-wide association studies (GWAS) from the past several years have provided the first unbiased evidence of the genes contributing to common cardiovascular disease traits in European and some Asian populations. The results not only confirmed the importance of prior knowledge, such as the central role of lipoproteins, but also revealed that there is still much to learn about the underlying mechanisms of this disease, as most of the associated genes do not appear to be involved in pathways previously connected to atherosclerosis. In this review, I focus on the common forms of the disease and look at both human and animal model studies. I summarize what was known before GWAS, highlight how the field has been changed by GWAS, and discuss future considerations, such as the limitations of GWAS and strategies that may lead to a more complete, mechanistic understanding of atherosclerosis.