On October 10, 2014, the Office of Science and Technology Policy (OSTP) announced that the President’s Council of Advisors on Science and Technology (PCAST) released the Report to the President and Congress on the Fifth Assessment of the National Nanotechnology Initiative, which concludes that the nanotechnology community is at an important turning point. PCAST recommends that the federal government accelerate its activities aimed at facilitating the commercialization of federally sponsored research, “thereby enabling the Nation to reap the benefits of this investment.” To help focus the commercialization process, PCAST calls for the nanotechnology community to take on a series of national nanotechnology Grand Challenges. Specific nanotechnology Grand Challenges would provide a way to turn scientific advances into products that leverage existing opportunities and meaningfully address existing needs. In the report, PCAST recommends that the federal government establish and execute a process for engaging the nanotechnology community to identify specific Grand Challenges that best support these goals. PCAST also provides some specific recommendations regarding the formulation of the Grand Challenges and innovation prizes and public-private partnerships to support them, as well as a focus on manufacturing challenges. Finally, the report details several program management updates to leadership initiatives, advisory input, evaluation metrics, and other areas to ensure the continuing success of the National Nanotechnology Initiative.