Seeking to develop cultural institutions, citizens (notably town trustee and future United States Secretary of the Treasury James Guthrie) called for a medical school to be founded in Louisville.

[7] Classes at the Louisville Medical Institute began in temporary quarters in fall 1837, eventually moving to a building designed by Kentucky architect Gideon Shryock eight months later.

By the early 1840s, University of Louisville School of Medicine had become a distinguished center for medical education, attracting students from a wide variety of locations in the southern and western United States.

Many notably physicians and researchers became affiliated with the medical department, including Daniel Drake, Charles Wilkins Short, J. Lawrence Smith, Benjamin Silliman, and David Wendel Yandell.

University officials began construction of a Health Sciences Center, where health-related study and research would take place and the School of Medicine would be located.

Vice President for health affairs Harold Boyer oversaw state appropriation of funds for the construction of a new teaching hospital and ambulatory care center.

Notably, the University of Louisville housed the world's first emergency room, opened in 1911 and developed by surgeon Arnold Griswold in the 1930s.

[16] In 1998, Dr. Roberto Bolli led a U of L team that identified an intracellular molecule that could protect the heart from ischemic myocardial damage.

[17] NIH reviewers rated the proposed research program as exceedingly innovative and potentially high-impact, noting that it addresses an extremely important clinical problem in a way that will move treatments from the laboratory to the patient as quickly as possible.

The resulting paper was retracted by The Lancet for data falsification,[19] He is or has been on the editorial board of all major cardiovascular journals and was the Editor in Chief of Circulation Research, a post from which he was dismissed for making homophobic comments He has been a member of numerous NIH study sections and committees and is a member of the NHLBI Advisory Council.

Out of state seats are awarded to those with superior academic achievement, MCAT scores, research, community service and/or ties to Kentucky.