Trustworthiness is the cornerstone professional virtue in the practice of medicine. The authors' goals for this Invited Commentary were to provide an account of the professional virtue of trustworthiness and its historical origins as well as to suggest how trustworthiness in a professional curriculum can be taught and assessed. They identified 2 components of trustworthiness that originate in the work of John Gregory (1724-1773) and Thomas Percival (1740-1804), who invented the ethical concept of medicine as a profession. The first is intellectual trust, the commitment to scientific and clinical excellence. The second is moral trust, the primary commitment of physicians and health care organizations to promote and protect the interest of patients while keeping individual and group interests secondary. Teaching should focus first on the mastery and understanding of the conceptual vocabulary of intellectual and moral trust through a range of formats, including modeling by faculty on how they respect and treat patients and learners. Assessment should be behaviorally based and articulated in increasing, observable, and integrated levels of mastery through training. Medical educators and academic leaders also share the responsibility to inculcate and sustain an organizational culture of professionalism that is respectful, critically self-appraising, accountable, and committed to its learners and to the promotion of physician well-being. These proposals can be used by medical educators and academic leaders to assist learners to become and remain trustworthy physicians.