In recent years, there have been multiple publications about the dearth of Black men in medicine. Appreciating the fact that underrepresented minority physicians disproportionately care for America's underserved communities, the lack of diversity in health care is particularly disturbing. Of imminent concern is the critical shortage of Black men doctors. In this Perspective, the authors contend that while mentoring is often considered among the most important strategies to increase the number of Black men in medicine, unique challenges in this demographic can diminish its effectiveness. Among these challenges are below average primary school educational experiences and a general mistrust of society on the part of Black men, as well as difficulties overcoming stereotypes and social biases that others hold against them. Furthermore, acknowledging that mentorship is paramount in achieving success in the medical field, the authors provide a framework to assist mentors in recognizing and addressing situations and obstacles that may disrupt the mentoring relationship and hinder its potential to best serve Black men pursuing advancement in medicine. This framework is represented by the acronym RACE: Reluctance to discuss race, Access to mentors, Cultural mistrust and racial concordance, and Empathy.