The goal of the National Heart, Lung, and Blood Institute’s (NHLBI) Trans-Omics for Precision Medicine (TOPMed) program is to generate large scale genomic data resources that will enable investigators to generate new knowledge to improve the understanding of heart, lung, blood, and sleep disorders and advance precision medicine of related conditions. The TOPMed program was initiated in 2014, has generated whole genome sequencing data (WGS) for over 160,000 individuals, and will soon exceed 100,000 assessments of multi-Omics (RNA-seq, methylome, metabolome, and proteome) data. TOPMed spans more than 90 NHLBI cohorts and clinical studies, over 1,000 investigators, 32 phenotype-focused working groups, 10 committees, and 4 sequencing centers.