The United States’ national scientific user facilities provide unique capabilities, instrumentation, and expertise annually to approximately 50,000 scientists and engineers from academia, government, and industry. For many of these individuals, a user facility is their laboratory—their primary platform for experimental research—and they gain access to these unique tools through peer-reviewed proposals. Much of the research is basic (discovery) research, but the rich interdisciplinary environment promotes interactions among scientists from diverse fields, institutional types, and countries to facilitate the translation of these discovery findings into solutions to real-world problems. This symposium provides an overview of the capabilities offered by these national facilities and highlights outstanding recent examples of discovery and innovation stemming from work at the user facilities, including the development of energy-harvesting “solar shingles,” the discovery of the structure of key biological molecules, the development of new drugs, and the discovery and the contributions to our understanding of fundamental science. The symposium includes presentations by the major federal sponsors of the user facilities with time for discussion of the policy challenges facing this key facet of the U.S. scientific enterprise now and into the future.