In 2005, USAID and the U.S. President´s Emergency Plan for AIDS Relief (PEPFAR), created the Supply Chain Management System (SCMS) to procure and distribute essential medicines and supplies; provide technical assistance to transform existing supply chains; and collaborated with in-country and global partners to coordinate efforts. The new US Global Health Initiative (GHI) initialized in 2010 sought to build on these efforts through strengthened platforms and systems. PEPFAR's five-year strategy, as contribution to the GHI, focused on transitioning the program from an emergency response to a sustainable, country-owned effort. The case describes the general approach designed by SCMS, the intricacies of its successful implementation in Ethiopia, and the challenges moving forward in that country.