Global advances in medicine, food, water, energy, microelectronics, communications, defense, and other important sectors of the economy are increasingly driven by discoveries in nanoscience and the development of nanotechnologies. Engaging the nanoscience and technology community in the crafting of national priorities, developing novel approaches for translating fundamental discovery to a technology readiness level appropriate for venture/industry funding, increasing domestic student interest in nanoscience to expand the workforce pipeline, and exploring new ways of coordinating the work of the National Nanotechnology Initiative (NNI) are all imperatives if the United States is to fully reap the societal benefits of nanotechnology. A Quadrennial Review of the National Nanotechnology Initiative provides a framework for a redesign of the NNI and its coordination with the goal of achieving a U.S. resurgence in nanotechnology. This report makes recommendations to improve the value of the NNI's research and development strategy and portfolio to the economic prosperity and national security of the United States.