On August 29, 2007, a century of exclusively not-for-profit undergraduate medical education in the United States ended, with the provisional accreditation of investor-owned Rocky Vista University College of Osteopathic Medicine.1 On September 5, 2014, in a first for allopathic medicine, the Ponce Health Sciences University School of Medicine, a 35-year-old not-for-profit institution in financial distress, was acquired by Arist Medical Sciences University, a for-profit public benefit corporation.2 More recently, investor-owned California Northstate University College of Medicine and Burrell College of Osteopathic Medicine received preliminary and provisional accreditation, respectively.3,4 Collectively, these for-profit medical schools now account for 495 matriculants in the class of 2020. Additional for-profit medical schools are expected. In this Viewpoint, we trace the accreditation history of for-profit medical schools, discuss the challenges facing these new entrants, explore their potential contributions to the medical education enterprise, and examine their future.