ABSTRACT Physicians well-trained to identify and treat patients with unhealthy substance use continue to be in short supply; this is an acute need in the setting of the ongoing overdose epidemic. Advancing research and training that would strengthen the clinical and research skills of physicians who are on the front lines of the current addiction epidemic is our aspirational goal. These physicians are generalist physicians caring for patients from adolescence through adulthood who are experiencing unhealthy substance use and subspecialty physicians caring for patients with HIV and Hepatitis C virus infection. This renewal application proposes funding for years 21-25 (2022-2027) of the Clinical Addiction Research and Education (CARE) Program to expand upon previous successes to develop substance use disorder expertise among physician researchers and educators. The CARE Program has the following Specific Aims: To carry out (1a) CRIT (Chief Resident Immersion Training) – immersion training in Addiction Medicine to educate Chief Residents (CRs) to teach state-of-the-art clinical care of patients with substance use; (1b) CARE Faculty Scholars Program – training for residency program faculty to incorporate Addiction Medicine content into their residency program training, mentor other faculty in this realm in their medical school and improve addiction services at their institution; (2) FIT (Fellow Immersion Training) – immersion training in Addiction Medicine in order to prepare clinical subspecialty fellows, including Adolescent Medicine, Infectious Disease, and Gastroenterology to incorporate substance use topics into their research; and (3) PRiT (Physician Researchers in Training) – mentored experiences to expose medical trainees and support early career physician faculty in the development of clinical addiction research careers. The CARE Program faculty include NIDA-funded physician investigators experienced in both clinical research methods and the medical care of patients with or at risk for substance use disorders. The CARE Program components will make important contributions to the development of the next generation of diverse physician substance use researchers and to the dissemination of addiction research in order to provide better care for patients from adolescence through adulthood. These contributions will improve health outcomes, especially among groups whose unhealthy substance use is undertreated – such as African American, Hispanic, and Native American patients, as well as adolescents, resulting in reduced medical, social, and financial burdens of addiction.