Advances in human health require the efficient and rapid translation of scientific discoveries into effective clinical treatments; this process, in turn, depends on observational data gathered from patients, communities, and public health research that can be used to guide basic scientific investigation. Such bidirectional translational science, however, faces unprecedented challenges due to the rapid pace of scientific and technological development, as well as the difficulties of negotiating increasingly complex regulatory and commercial environments that overlap the research domain. Further, numerous barriers to translational science have emerged among the nation's academic research centers, including basic structural and cultural impediments to innovation and collaboration, shortages of trained investigators, and inadequate funding.To address these serious and systemic problems, in 2006 the National Institutes of Health created the Clinical and Translational Science Awards (CTSA) program, which aims to catalyze the transformation of biomedical research at a national level, speeding the discovery and development of therapies, fostering collaboration, engaging communities, and training succeeding generations of clinical and translational researchers. The authors report in detail on the planning process, begun in 2008, that was used to engage stakeholders and to identify, refine, and ultimately implement the CTSA program's overarching strategic goals. They also discuss the implications and likely impact of this strategic planning process as it is applied among the nation's academic health centers.