The introduction of science into the practice of medicine in the early 20th century was a transforming event for the profession. Now, breakthroughs in science and know how make it possible to transform care once again and to fix the broken U.S. health care system. To realize this potential, new models of prospective health care must be created and validated. Prospective health care would determine the risk for individuals to develop specific diseases, detect the disease's earliest onset, and prevent or intervene early enough to provide maximum benefit. Each individual would have a personalized health plan to accomplish this. Current knowledge is already sufficient to implement this approach, but there are no effective practice models, delivery systems, and appropriate reimbursement mechanisms. The authors describe the mechanisms of managing care prospectively, describe the components of a personalized health plan, and show how prospective care could relate to a community or group of covered individuals. They conclude by stressing that all interested parties, including academic health centers, insurers, and payers, will need to work together to develop innovative applications of new technologies and appropriate delivery models. At their own institution, pilot programs to foster prospective health care have already begun, and another initiative to develop models to use genomic medicine is also underway. Bipartisan political support will also be needed to help achieve rational reimbursement between providers and payers, so that prospective care can fulfill its promise of being the best cost-effective model to improve the nation's health.