“Leveraging Informatics to Enable Evidence-Generating Medicine and Create Learning Health Systems,” the 2019 Research Day keynote by Peter J. Embi, MD, MS, FACP, FACMI, focused on some fundamental challenges in the healthcare-research paradigm that drives our current systems. In this Brian L. Strom Visiting Professorship lecture, Dr. Embi, President and CEO of the Regenstrief institute and Leonard Betley Professor of Medicine, Indiana University School of Medicine, brought in his personal story as he discussed the key factors we must address in order to realize the vision of the learning health system.