Medical education in that era meant attending formal lectures for a semester or two, and being apprenticed to a practicing physician for several years. No academic preparation was required, no written exams were mandatory. Students did not pay tuition, but bought tickets to admit them to professor's lectures. Since no hospital existed for teaching, there was very little clinical training as part of the degree requirement.

The first three professors of the School were John Warren, Professor of Anatomy and Surgery; Benjamin Waterhouse, Professor of the Theory and Practice of Physic; and Aaron Dextor, Professor of Chemistry and Materia Medica. Benjamin Waterhouse had been educated at universities and hospitals in Europe. As a result of his contacts in England, he received a publication printed there in 1798 by Edward Jenner, reporting successful vaccination against smallpox. Waterhouse introduced Jenner's ideas to the U.S. medical community and first used the vaccine on members of his own family. As a result of Waterhouse's vigorous support of the smallpox vaccination, it was tested in Boston and gained acceptance in the U.S.

John Warren, a very skilled teacher and surgeon, was instrumental in moving the Medical School to Boston, where it was more convenient for the faculty to see their private patients as well as those in the dispensaries and military and naval hospitals that were being established in the city. In 1811, Warren's son, John Collins Warren, along with James Jackson, led efforts to start Massachusetts General Hospital. Since all those who had sufficient money were cared for at home, Massachusetts General Hospital, like most hospitals that were founded in the 19th century, was intended to care for the poor.

The Medical School moved from Cambridge to Boston in 1810, and has been there ever since. From 1816 to 1846, the School was on Mason Street, and because of a gift from the Great and General Court of Massachusetts to the School (a gift from a private bequest), the School was called the Massachusetts Medical College of Harvard University. In 1847 the School moved to North Grove Street, next door to the Bulfinch Building of Massachusetts General Hospital, and stayed there until 1883, when it relocated to Boylston Street in Copley Square, where the new wing of the Boston Public Library now stands.

President Eliot came to office in 1869, and in the few years following, he established a novel curriculum at the Medical School. Admissions standards were raised, written exams requiring passing grades were instituted, new departments of basic and clinical sciences were established, a three-year degree program was introduced, and the apprenticeship system was eliminated. Harvard Medical School became a professional school of Harvard University, setting the United States standard for the organization of medical education with a university.

In 1906, the Medical School moved to Longwood Avenue in Boston, and the five marble-faced buildings that compose the Quadrangle were dedicated. The Fenway was open farm and marshland when the Medical School moved there, and that combination of new school and empty land stimulated a migration of hospitals to the area.

The Medical School currently has six basic science departments: Biological Chemistry and Molecular Pharmacology, Cell Biology, Genetics, Microbiology and Molecular Genetics, Neurobiology, Pathology; two social science departments: Health Care Policy and Social Medicine; and a clinical department: Ambulatory Care and Prevention. Harvard Medical School has 18 affiliates, where most of the clinical training for interns, residents, and medical students occurs. The affiliates include Beth Israel Deaconess Medical Center, Brigham and Women's Hospital, Cambridge Hospital, Center for Blood Research, Children's Hospital, Dana-Farber Cancer Institute, Joslin Diabetes Center, Judge Baker Children's Center, Massachusetts Eye and Ear Infirmary, Massachusetts General Hospital, Massachusetts Mental Health Center, McLean Hospital, Mount Auburn Hospital, New England Regional Primate Center, Schepen's Eye Research Institute, Spaulding Rehabilitation Hospital, and Veterans Administration Medical Center.

For over two centuries Harvard Medical School has been a major participant in the effort to understand life, to cure and prevent disease, and to reduce the burden of human illness. The School is a place of 'firsts.' Since the introduction of the small pox vaccination to America in 1799 by Professor Waterhouse, Harvard Medical School faculty have discovered, innovated, and made giant steps toward improving human health and medical practice. The first introduction of insulin to the U.S. was made by Harvard Medical School researchers. The iron lung was invented for polio patients; then work on the polio virus, done at the Medical School, paved the way for vaccines against polio, and made the iron lung obsolete. Other innovations include mapping the visual system of the brain, development of the external cardiac pacemaker, development of artificial skin, the first successful kidney transplant, initial use of direct electric current to restore the rhythm of the heart, and discovery of the gene that causes Duchenne Muscular Dystrophy.