Introduction: In academic health centers, the number of physician investigators and the number of research studies headed by clinicians has been declining. The U.S. Institute of Medicine and the National Institutes of Health suggest improved mentoring is important to reversing these trends. Methods: This is a case study review of the role of mentors in developing and sustaining clinical investigators at the Cleveland Clinic. Results: Issues influencing mentoring relationships at the Cleveland Clinic include whether mentoring contracts are formally or informally related and are agreed on; whether there are scheduled meetings for mentors and proteges; whether there are clearly articulated benchmarks and manageable steps; and whether there is a code of mentorship. Conclusions: Interactive group formats can lead to development of a code of mentorship and increased awareness of faculty regarding clinical investigation.