For several decades, a barrier has existed between research and clinical medicine, making it difficult for aspiring scientists to gain exposure to human pathophysiology and access to clinical/translational research mentors during their graduate training. In 2005, the Howard Hughes Medical Institute announced the Med Into Grad initiative to support graduate programs that integrate clinical knowledge into PhD biomedical training, with the goal of preparing a new cadre of translational researchers to work at the interface of the basic sciences and clinical medicine. Two institutions, Baylor College of Medicine and the Cleveland Clinic/Case Western Reserve University, developed new PhD programs in translational biology and/or molecular medicine. These programs teach the topics and skills that today’s translational researchers must learn and expose students to clinical medicine. In this article, the authors compare and contrast the history, implementation, and evaluation of the Translational Biology and Molecular Medicine program at Baylor College of Medicine and the Molecular Medicine program at the Cleveland Clinic/Case Western Reserve University. The authors also demonstrate the feasibility of creating a multidisciplinary graduate program in molecular medicine that integrates pathophysiology and clinical medicine without extending training time. They conclude with a discussion of the similarities in training approaches that exist despite the fact that each program was independently developed and offer observations that emerged during their collaboration that may benefit others who are considering developing similar programs.