The goal of systems biology is to define all of the elements present in a given system and to create an interaction network between these components so that the behavior of the system, as a whole and in parts, can be explained under specified conditions. The elements constituting the network that influences the development of atherosclerosis could be genes, pathways, transcript levels, proteins, or physiologic traits. In this review, we discuss how the integration of genetics and technologies such as transcriptomics and proteomics, combined with mathematical modeling, may lead to an understanding of such networks.