Most male professionals have more experience mentoring men than they do mentoring women, and their male mentees progress further than their female mentees. Yet, in academic medicine, men have few forums in which to discuss the gender-related issues that they encounter. To address the gender-related questions that commonly arise, the author of this commentary offers perspectives and recommendations, consolidated from over 25 years of experience leading career and talent development programs, to assist men in successfully mentoring women. Her recommendations are organized around three questions: (1) How do women’s and men’s experiences in mentoring relationships tend to differ? (2) What interferes with the accurate evaluation of women’s skills? and (3) Is the current generation of female trainees still at a gender-related disadvantage? She argues that men’s ability to effectively mentor women depends to a great extent on their understanding of the challenges that women disproportionately face in developing their careers. Mentors who are skilled in adapting to the gender-related needs of mentees will contribute to women’s retention and development in academic medicine, enhance the leadership capacity of their organizations and the profession, and extend their own legacies.