Academic medical center (AMC) faculty, administrators, and leaders have the critical tasks of teaching and training the next generation of health care providers and biomedical researchers, as well as generating new knowledge that improves the health of all. In the United States, medical schools and their affiliated hospitals train remarkably high-quality physicians and scientists, and the research conducted at these institutions results in advances in health. To that end, AMCs have become essential engines for driving better health in the United States and the rest of the world; they also have become essential engines driving the economies of their respective communities and regions. The education and research missions, however, require subsidization because tuition and extramural grant funding do not cover the costs of these endeavors. This subsidization largely has come from revenues generated by AMCs' clinical endeavors. The viability of this cross-subsidization, however, is increasingly threatened in the current clinical environment. The authors of this Perspective discuss these issues in depth and provide some concrete recommendations to address these challenges. They hope to stimulate discussion and, ultimately, ensure the financial viability of U.S. AMCs-a national resource of utmost importance. Recommendations to sustain research include creating strategic biomedical research plans, developing a defined and sustained model to support National Institutes of Health funding that keeps pace with inflation, and evolving funding mechanisms. Recommendations to sustain medical education include limiting student debt, creating more cost-effective curricula, and ensuring that clinical training opportunities that meet national standards are available to students.