Simon Flexner, M.D. (March 25, 1863 in Louisville, Kentucky – May 2, 1946) was a physician, scientist, administrator, and professor of experimental pathology at the University of Pennsylvania (1899 – 1903). He was the first director of the Rockefeller Institute for Medical Research (1901 – 1935) and a trustee of the Rockefeller Foundation. He was also a friend and advisor to John D. Rockefeller, Jr.. He was the elder brother of Abraham Flexner and of the Zionist leader Bernard Flexner

Amongst Flexner's most important achievements are studies into poliomyelitis and the development of serum treatment for meningitis.

The bacteria species Shigella flexneri was named in recognition of Flexner. In addition, Flexner was the first to describe Flexner - Wintersteiner rosettes, a characteristic finding in retinoblastoma. His son James Thomas Flexner was a prolific writer; one of his works was an extensive biography of George Washington.

Dr. Flexner died in May 1946 in New York City, from a myocardial infarction (heart attack). He was 83 years old. His papers are currently housed at the American Philosophical Society.