The early success of the President's Emergency Plan for AIDS Relief (PEPFAR) in delivering antiretroviral medications in poor countries unmasked the reality that many lacked sufficient health workers to dispense the drugs effectively. The 2008 reauthorization of PEPFAR embraced this challenge and committed to supporting the education and training of thousands of new health workers. In 2010 the program, with financial support from the US National Institutes of Health and administrative support from the Health Resources and Services Administration, launched the Medical Education Partnership Initiative to fund thirteen African medical schools and a US university. The US university would serve as a coordinating center to improve the quantity, quality, and retention of the schools' graduates. The program was not limited to training in the delivery of services for patients with HIV/AIDS. Rather, it was based on the principle that investment in medical education and retention would lead to health system strengthening overall. Although results are limited at this stage, this article reviews the opportunities and challenges of the first year of this major transnational medical education initiative and considers directions for future efforts and reforms, national governmental roles, and the sustainability of the program over time.