The Carnegie Foundation for the Advancement of Teaching, which in 1910 helped stimulate the transformation of North American medical education with the publication of the Flexner Report, has a venerated place in the history of American medical education. Within a decade following Flexner's report, a strong scientifically oriented and rigorous form of medical education became well established; its structures and processes have changed relatively little since. However, the forces of change are again challenging medical education, and new calls for reform are emerging. In 2010, the Carnegie Foundation will issue another report, Educating Physicians: A Call for Reform of Medical School and Residency, that calls for (1) standardizing learning outcomes and individualizing the learning process, (2) promoting multiple forms of integration, (3) incorporating habits of inquiry and improvement, and (4) focusing on the progressive formation of the physician's professional identity. The authors, who wrote the 2010 Carnegie report, trace the seeds of these themes in Flexner's work and describe their own conceptions of them, addressing the prior and current challenges to medical education as well as recommendations for achieving excellence. The authors hope that the new report will generate the same excitement about educational innovation and reform of undergraduate and graduate medical education as the Flexner Report did a century ago.