Recent scientific and technological innovations presage a future wherein heart, lung, blood, and sleep (HLBS) health threats are preempted and wherein precision medicine reduces the burden of HLBS disease. The research priorities of the National Heart, Lung, and Blood Institute (NHLBI) Strategic Vision guide Institute activities toward this future. To realize the Strategic Vision, NHLBI has drawn upon its rich resources, including its cohort studies, clinical trial infrastructure, and precision medicine programs. Strategic Vision implementation also requires leveraging datasets of scale and scope expansive enough to deconstruct the complexity of human biology and disease. The large platform of participants and datatypes in the All of Us Research Program (All of Us) facilitates exploration of scientific questions towards improved knowledge, prevention, and management of HLBS conditions. Here, we discuss how utilizing All of Us has stimulated novel HLBS research and provide examples of future research that can be conducted via this platform. Overall, Strategic Vision implementation through All of Us will elucidate how biology, lifestyle, and social and physical environment influence health and disease
deepen understanding of population and individual differences or disparities
and accelerate development, implementation, and dissemination of targeted diagnostic, prevention, and treatment strategies for HLBS conditions.