Molecular biophysics at the University of Pennsylvania has a long and rich history. Eldridge Reeves Johnson, the former president of the Victor Talking Machine Company (RCA), gave the University a generous endowment in 1927 to establish a foundation in medical physics. The Johnson Foundation (JF) was dedicated to the "study and development of physical methods in the investigation of disease and in its cure". The JF was the first organization in this country dedicated to biophysics. Under the leadership of Detlev Bronk, investigators developed and expanded methods for recording action potentials in nerves, developed innovative techniques of oxygen electrode measurements, and explored new technologies such as ultrasound and electron microscopy. Under the leadership of Britton Chances optical methods were pioneered at Penn to study cell organelles and tissues. In addition, research in the JF mapped out much of the molecular machinery of respiration and energy metabolism. The JF was also instrumental in pioneering the use of nuclear magnetic resonance spectroscopy to visualize biochemical processes in intact tissues. The Johnson Foundation, now under the direction of P. Leslie Dutton, has continued to evolve and expand into structural and computational biology, high resolution NMR spectroscopy, and protein folding. True to the mandate of the Johnson Foundation, biophysical methodologies are being used to explore fundamental processes that are vital to human biology and disease. RELEVANCE: The training program in Structural Biology and Molecular Biophysics at the University of Pennsylvania promotes the application of biophysics to clinically relevant research. The fundamental goal of our training mission is to produce biophysicists who can effectively integrate and apply the physical methodologies to medically relevant research problems. Our program explicitly integrates human biology and pathology into the graduate curriculum. The SBMB training program is designed to produce well-rounded scientists with expertise in structural biology and biophysics as well as have a solid foundation biomedical sciences and disease.