In 1945, Vannevar Bush published Science: The Endless Frontier and thereby established an intellectual architecture that has largely defined public science institutions and policy since. In this NBER volume, we take stock of the science and innovation environment today and consider two key questions: (1) what are critical dimensions of change in science and innovation systems since Vannevar Bush articulated his vision, and (2) what are the implications of these changes for policies and institutions in the years and decades ahead? The Changing Frontier has twelve chapters in four parts. Part I investigates the organization of scientific research, especially the increasingly dominant role of teamwork. Part II examines shifts in the geography of scientific research and connects to a broader literature suggesting that geographic agglomeration remains an enduring feature of innovative activity. Part III considers market-based innovation, emphasizing new modes of entrepreneurship in mobile applications and clean energy, while also considering state-level entrepreneurship policies. Part IV investigates the evolution of science institutions in the light of Bush’s initial vision, and then considers how science-innovation linkages have shifted with the nature of technology. This volume brings together in one place many important changes in the nature of science and innovation, and articulates the interplay between science and innovation practice and public science institutions and policy.