The continuum of clinical and translational science encompasses the broadest vision of how medical research and healthcare can be transformed locally and globally to maximize the benefits of innovation for the greatest number of people. The NIH Roadmap and NCRR CTSA program have been developed to improve the efficiency and effectiveness along that continuum by changing the culture and practice of the biomedical research enterprise. A national network of CTSA-funded institutes is already revolutionizing how research is practiced, with expectations that innovation will accelerate, new collaborations will emerge, and health care solutions for intractable problems will evolve. This CTSA application from the Delaware Valley Institute of Clinical and Translational Sciences (DVICTS) addresses challenges that limit the nation’s biomedical research enterprise and that are evident in the region it serves. DVICTS takes the broad vision and applies it in a regional setting that has special requirements and resources. This combination offers opportunities to conduct clinical and translational research projects that have direct bearing on intractable national health problems, since DVICTS can closely study a population that represents U.S. demographics. DVICTS has begun this effort by bringing together organizations with complementary missions and resources, creating a single home for clinical and translational science. The Philadelphia-based academic medical center Thomas Jefferson University (TJU), heart of the largest regional healthcare system, is home to physician scientists focused on T0-T2 translation. Nemours is one of the largest pediatric networks and research organizations in the country, providing pediatric care across four states, with its home base at Alfred I. DuPont Hospital for Children (Nemours/ AIDHC) in Wilmington, Del., the pediatric hospital for TJU. Christiana Care Health System (CCHS), the largest provider of healthcare service, research and education in Delaware, is focused on community-engaged outcomes- and participant-based research supporting T3 translation. The University of Delaware (UD) is the largest institution for education and research in the state and the academic home of a 2010 Nobel Prize winner in Chemistry, Richard F. Heck. It is poised to recruit, train, and retain the diversified workforce needed to build the next generation of clinical and translational research teams. These resources are complemented by unparalleled biomedical informatics opportunities represented by the Delaware Health Information Network (DHIN), the first statewide, electronic health information exchange in the country, managing >15 million patient transactions/month, linking CCHS with two other hospital systems, 620 physicians, and 100 practices throughout Delaware. Similarly, Nemours/AIDHC deploys NemoursOne, an electronic health records system that recently won the Davies Organizational Award for excellence in this area. These tools can capture all patient exchanges across all practices and hospitals in Delaware, creating the first state-wide “living laboratory.” Consolidating these operations in DVICTS creates a regional organization that integrates stand-alone institutional resources, enabling an unmatched pipeline for (1) discovery-development-application-dissemination and (2) training across the educational continuum, from undergraduates to faculty, supported by cross-institutional administration to generate regional and national health care innovation.