After a decade of rapid growth in average incomes, many countries have attained middle-income country (MIC) status. This paper examines the implications of this ‘new bottom billion’ for global health efforts and recommends a tailored middle-income strategy for the Global Fund and GAVI. The paper describes trends in the global distribution of poverty, preventable infectious diseases, and health aid response to date; revisits the rationale for health aid through agencies like GAVI and the Global Fund; and proposes a new MIC strategy and components, concluding with recommendations.