Cleveland Clinic Lerner College of Medicine (CCLCM) is an innovative, five-year medical education track within Case Western Reserve University School of Medicine (Case) with a focused mission to attract and educate a limited number of highly qualified persons who seek to become physician investigators. CCLCM curriculum governance, faculty appointments and promotions, and admissions committees are integrated with respective Case committees. The CCLCM curriculum is based on faculty-defined professional attributes that graduates are expected to develop. These attributes were used to create curricular and assessment principles that guided the development of an integrated basic science, clinical science, and research curriculum, conducted in an active learning environment. An organ-system approach is used to solidify an understanding of basic science discipline threads in the context of relevant clinical problems presented in PBL and case-based discussion formats. Clinical skills are introduced in the first year as part of the two-year longitudinal experience with a family practice or internal medicine physician. The research program provides all students with opportunities to learn and experience basic and translational research and clinical research before selecting a research topic for their 12- to 15-month master-level thesis project. All Case students participate in required and elective clinical curriculum after the second year, but CCLCM students return to the Cleveland Clinic on selected Friday afternoons for program-specific research and professionalism-learning activities. A unique portfolio-based assessment system is used to assess student achievements in nine competency areas, seven of which reflect the Accreditation Council for Graduate Medical Education competencies.