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Abstract Almost half of all countries in the world are effectively free of human deaths from dog-mediated rabies. But the disease still affects people in low- and middle-income countries, especially the rural poor, and children. Successful regional elimination of human rabies is attributable to advances in significant and sustained investment in dog vaccination, post-exposure vaccination and surveillance, illustrated by productive efforts to reduce human rabies in Latin America over the last 35 years. Nonetheless, countries still facing endemic rabies face significant barriers to elimination. Using the 2017 Global Strategic Plan to end human rabies deaths from dog-mediated rabies by 2030 as a reference point and an organizing framework, we assess progress toward global rabies elimination by examining the characteristics of successful regional control efforts and barriers to elimination. Although substantive barriers exist for countries where rabies remains endemic, advances in knowledge, technology, institutions, and economics provide a basis for optimism.