Coronary heart disease (CHD) will soon become the leading cause of death and morbidity in the world. Early detection and treatment of CHD is thus imperative to improve global health. Atherosclerosis of the coronary arteries is a complex multifactorial disease process involving multiple pathways that can be influenced by both genetic and environmental factors. With the recent advances in genomics and proteomics, many new risk factors with small-to-moderate effects are likely to be identified. Additionally, individualized risk stratification and targeted therapy may become feasible; each individual could potentially be assessed with a panel of tests for genomic and proteomic markers and, on the basis of the individual's composite risk profile, preventive and therapeutic steps could then be undertaken. With a multimarker approach, it may also be possible to identify alterations in pathways involved in atherogenesis, rather than focus on individual risk factors. In this article, we use the specific example of atherosclerosis to discuss the role of genomics and proteomics in cardiovascular risk assessment.