Circulating levels of blood lipids are heritable risk factors for atherosclerosis and heart disease, and are the target of therapeutic intervention. Studies of monogenic disorders and – more recently – genome-wide association studies have identified several important genetic determinants of blood lipid levels. These have the potential to provide new drug targets to alter blood lipid levels and may improve prediction of cardiovascular disease. Better functional validation of lipid loci is required to clarify the biological role of proteins encoded by specific genomic regions and understand how they influence lipid metabolism and confer disease risk.