The U.S. scientific enterprise has produced countless discoveries that have led to significant advances in technology, health, security, safety, and economic prosperity. However, concern exists that excessive, uncoordinated, and duplicative policies and regulations surrounding research are hampering progress and jeopardizing American scientific competitiveness. Estimates suggest the typical U.S. academic researcher spends more than 40 percent of their federally funded research time on administrative and regulatory matters, wasting intellectual capacity and taxpayer dollars. Although administrative and regulatory compliance work can be vital aspects of research, the time spent by researchers on such activities continues to increase because of a dramatic rise in regulations, policies, and requirements over time.To better ensure that the research community is maximally productive while simultaneously ensuring the safety, accountability, security, and ethical conduct of publicly funded research, Simplifying Research Regulations and Policies: Optimizing American Science examines current federal research regulations. This report identifies ways to improve regulatory processes and administrative tasks, reduce or eliminate unnecessary work, and modify and remove policies and regulations that have outlived their purpose while maintaining necessary and appropriate integrity, accountability, and oversight. Simplifying Research Regulations provides a roadmap for establishing a more agile and resource-effective regulatory framework for federally funded research.