The story of Abraham Flexner's role in the founding of the Institute for Advanced Study in Princeton, New Jersey, offers important insights into Flexner himself and valuable lessons for contemporary leaders in academic medicine. The authors review this remarkable achievement along with Flexner's other accomplishments in the 49 years he lived after the 1910 publication of his report on medical schools in the United States and Canada. Lessons include his approach to philanthropy, his determination and networking, his belief in the synergism between the natural sciences and the humanities, and his regard for learning as a lifelong process. Flexner's record was not unblemished, however, and the cases in which he faltered also offer important lessons for today's academic leaders.