Fueled by the rapid pace of discovery, humankind's ability to understand the ultimate causes of preventable common disease burdens and to identify solutions is now reaching a revolutionary tipping point. Achieving optimal health and well-being for all members of society lies as much in the understanding of the factors identified by the behavioral, social, and public health sciences as by the biological ones. Accumulating advances in mathematical modeling, informatics, imaging, sensor technology, and communication tools have stimulated several converging trends in science: an emerging understanding of epigenomic regulation; dramatic successes in achieving population health-behavior changes; and improved scientific rigor in behavioral, social, and economic sciences. Fostering stronger interdisciplinary partnerships to bring together the behavioral-social-ecologic models of multilevel "causes of the causes" and the molecular, cellular, and, ultimately, physiological bases of health and disease will facilitate breakthroughs to improve the public's health. The strategic vision of the Office of Behavioral and Social Sciences Research (OBSSR) at the National Institutes of Health (NIH) is rooted in a collaborative approach to addressing the complex and multidimensional issues that challenge the public's health. This paper describes OBSSR's four key programmatic directions (next-generation basic science, interdisciplinary research, systems science, and a problem-based focus for population impact) to illustrate how interdisciplinary and transdisciplinary perspectives can foster the vertical integration of research among biological, behavioral, social, and population levels of analysis over the lifespan and across generations. Interdisciplinary and multilevel approaches are critical both to the OBSSR's mission of integrating behavioral and social sciences more fully into the NIH scientific enterprise and to the overall NIH mission of utilizing science in the pursuit of fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to extend healthy life and reduce the burdens of illness and disability.