Precision medicine is poised to have an impact on patients, health care delivery systems and research participants in ways that were only imagined 15 years ago when the human genome was first sequenced. While discovery using genome-based technologies has accelerated, these have only begun to be adopted into clinical medicine. Here we define precision medicine and the stakeholder ecosystem required to enable its integration into research and health care. We explore the intersection of data science, analytics and precision medicine in creating a learning health system that carries out research in the context of clinical care and at the same time optimizes the tools and information used to delivery improved patient outcomes. We provide examples of real world impact, and conclude with a policy and economic agenda that will be necessary for the adoption of this new paradigm of health care both in the United States and globally