A new model for the conduct of clinical research was established at the University of Pennsylvania (Penn) School of Medicine, now the Perelman School of Medicine, through the development of the interdepartmental Center for Clinical Epidemiology and Biostatistics in 1993 and the basic science Department of Biostatistics and Epidemiology in 1994. The authors describe the development and evolution of these novel structures.Five key objectives were achieved with these structures' creation: (1) Clinical faculty have the opportunity to be identified as both clinicians and epidemiologists, (2) nonclinical faculty have an academic "home," (3) clinical trainees are now educated in population medicine, which promotes its incorporation into their clinical practice, (4) population medicine and clinical medicine have become fully integrated, and (5) better epidemiologic research is conducted, informed by clinical insights.Today's center is the primary home for epidemiology and biostatistics at Penn, linking epidemiology, biostatistics, clinical medicine, and the health sciences. The center's core faculty manage their own research programs, conduct primary research in epidemiology and biostatistics, serve as members of collaborative research teams, manage cores and service centers that support research projects, and lead graduate training programs in epidemiology and biostatistics. The department provides an academic home and structure for faculty, provides primary research in epidemiology and biostatistics, supports the center's mission, and provides training in biostatistics. This organizational approach has wide applicability across schools of medicine in the United States and abroad and has been a model for many.