Mentoring is beneficial to mentors, mentees, and their institutions, especially in low- and middle-income countries (LMICs), that are faced with complex disease burdens, skills shortages, and resource constraints. Mentoring in global health research can be enhanced by defining key competencies, to enable the skill set required for effective mentoring, determine training needs for local research mentors, and facilitate institutional capacity building to support mentors. The latter includes advocating for resources, institutional development of mentoring guidelines, and financial and administrative support for mentoring. Nine core global health research mentoring competencies were identified: maintaining effective communication; aligning expectations with reasonable goals and objectives; assessing and providing skills and knowledge for success; addressing diversity; fostering independence; promoting professional development; promoting professional integrity and ethical conduct; overcoming resource limitations; and fostering institutional change. The competencies described in this article will assist mentors to sharpen their cognitive skills, acquire or generate new knowledge, and enhance professional and personal growth and job satisfaction. Similarly, the proposed competencies will enhance the knowledge and skills of mentees, who can continue and extend the work of their mentors, and advance knowledge for the benefit of the health of populations in LMICs.