The Undergraduate Medical Education for the 21st Century (UME-21) project evolved from two prior projects that were aimed at studying the interface between managed care and undergraduate medical education. The project provided funding for 18 US medical schools to demonstrate how they would produce graduates who eventually could practice in a rapidly changing health care environment. Medical schools were required to provide educational opportunities in nine content areas or outline why such educational opportunities could not be provided in their individual projects. Participating schools were chosen via an involved process after careful evaluation by a panel of experienced medical educators. In a project of this type, many lessons are learned. In the UME-21 project, lessons learned were gleaned from progress reports, participant annual reports, proceedings from annual project meetings and a National Symposium, findings of a National Education Group, and published papers. A lesson must have been reported by a least two involved schools to be included. The lessons learned were divided into six categories as follows: content areas, implementation, collaboration, evaluation, governance, implications-summary. Many lessons emanated from each of these categories; however, only the 10 most important lessons in each category are presented. The implications of the lessons learned are outlined and provide direction for the future of medical education innovation and research.