Coronary artery disease and its clinical manifestations, including myocardial infarction, are heritable traits, consistent with a role for inherited DNA sequence variation in conferring risk for disease. Knowledge of the new sequence variations in the genome that confer risk has the potential to illuminate new causal biologic pathways in humans and to thereby further improve diagnosis and treatment. Here, we review recent progress in mapping genetic loci related to coronary disease and risk factor phenotypes, including plasma lipoprotein concentrations. Genome-wide linkage (in families) and association (in populations) studies have identified more than a dozen genetic loci related to coronary disease. A key challenge now is to move from mapping loci to pinpointing causal genes and variants, and to develop a molecular understanding of how these genes lead to coronary disease.