The creation of the Clinical Translational Science Awards for academic health sciences campuses in 2006 was implicitly accompanied by a call for a new paradigm of faculty development and mentoring to train the next generation of researchers and leaders in this new approach to research. Effective mentoring is critical to help early-career investigators become successful, independent researchers, and a new approach to mentoring is vital to recruit, advance, and retain fellows and junior faculty engaged in clinical and translational research. However, in addition to the many rewards of mentoring, there are numerous substantive barriers to effective mentoring. These barriers include a lack of training in how to be a mentor, lack of time and structural and financial support for mentoring, and competing personal, administrative, and clinical demands. The authors describe an innovative program, the University of California, San Francisco Mentor Development Program (MDP), established in 2006 and designed to train midcareer academic health sciences researchers to be more effective as clinical and translational research mentors. Using a framework for presenting innovations in academic research, they present the rationale, design, implementation, and mechanisms being used to evaluate and sustain the MDP. Specific details of the objectives and content of the MDP sessions are provided as well as evaluation criteria and a link to specific curriculum materials.