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In 1910, in his recommendations for reforming medical education, Abraham Flexner responded to what he deemed to be the “public interest.” Now, 100 years later, to respond to the current needs of society, the education of physicians must once again change. In addition to understanding the biological basis of health and disease, and mastering technical skills for treating individual patients, physicians will need to learn to navigate in and continually improve complex systems in order to improve the health of the patients and communities they serve. Physicians should not be mere participants in, much less victims of, such systems. Instead, they ought to be prepared to help lead those systems toward ever-higher-quality care for all. A number of innovative programs already exist for students and residents to help integrate improvement skills into professional preparation, and that goal is enjoying increasing support from major professional organizations and accrediting bodies. These experiences have shown that medical schools and residency programs will need to both teach the scientific foundations of system performance and provide opportunities for trainees to participate in team-based improvement of the real-world health systems in which they work. This significant curricular change, to meet the social need of the 21st century, will require educators and learners to embrace new core values, in addition to those held by the profession for generations. These include patient-centeredness, transparency, and stewardship of limited societal resources for health care.