A major goal of the Medical Education Partnership Initiative (MEPI) is to improve local health systems by strengthening medical education in Sub-Saharan Africa. A new approach to collaboration was intended to overcome the one-sided nature of many partnerships that often provide more rewards to institutions from wealthy countries than to their Sub-Saharan African counterparts. The benefits of this MEPI approach are reflected in at least five positive outcomes. First, effective partnerships have been developed across a diverse group of MEPI stakeholders. Second, a "community of practice" has been established to continue strengthening medical education in Sub-Saharan Africa. Third, links have been strengthened among MEPI health science schools in Sub-Saharan Africa, their communities, and ministries of both health and education. Fourth, respect among partners in the United States for a culture of ownership and self-determinism among their African counterparts committed to improving education has been enhanced. And finally, performance metrics for strengthening of health science education in Sub-Saharan Africa have been advanced. Meanwhile, partner medical schools in the United States have witnessed the benefits of collaborating across traditional disciplinary boundaries, such as physicians working within highly functioning community-based health care teams with many of the participating schools in Sub-Saharan Africa. MEPI demonstrates that North-South as well as South-South partnerships, with an explicit focus on improving local health systems through better education, can be designed to empower partners in the South with support from collaborators in the North.