The inaugural issue of Circulation: Cardiovascular Ge-netics arrives at a remarkable time in the history of genetic research and cardiovascular medicine. Despite tremendous progress in knowledge gained, cardiovascular disease (CVD) remains the leading cause of death in the United States, 1 and it has overcome infectious diseases as the leading cause of death worldwide. 2 In addition, rates of CVD remain higher in black and Hispanic populations in the United States. 1 The recent Strategic Plan of the National Heart, Lung, and Blood Institute (NHLBI) emphasizes research areas to fill the significant knowledge gaps needed to improve the diagnosis, treatment, and control of known risk factors and clinically apparent disease. Simultaneously, the NHLBI Strategic Plan recognizes a tremendous opportunity that is available for use of genetic and genomic research to generate new knowledge that might reduce the morbidity and mortality from CVD in US populations. 3 Public availability of vast amounts of detailed sequence information about the human genome, completed sequence data on dozens of other animal genomes, and private sector development of high-throughput genetic technologies has transformed in a few short years the conduct of cardiovascular genetics and genomics research from a primary focus on mendelian disorders to a current emphasis on genome-wide association studies (GWAS; Figure 1). In this review, we describe the rationale for the current emphasis on large-scale genomic studies, summarize the evolving approaches and progress to date, and identify immediate-term research needs. The National Institutes of Health (NIH) and the NHLBI are supporting a portfolio of large-scale genetic and genomic programs in diverse US populations with the longer-term objective of translating knowledge into the prediction, prevention, and preemption of CVD, as well as lung, sleep, and blood disorders. Underlying this portfolio is a strong commitment to make available participant-level data and aggregate research results to the broad community of investigators, while protecting the privacy and confidentiality and respecting the informed consent of study participants.