Responding to public health challenges at the global and local levels can give rise to an array of tensions. To assure sustainable public health, these tensions need to be meaningfully balanced. Using empirical evidence and lived experiences relating to HIV from the global south, this book enunciates the many dimensions of national-level responses to HIV/AIDS including conceptual, philosophical, and methodological perspectives from public health, public policy, bioethics, and social sciences. Calling out glaring neglects, the book makes a bold recommendation for the destabilization of the naturalness with which national HIV/AIDS responses ignore the socio-political and medico-ethical dimensions of HIV. The case made is grounded in the philosophy of social public health. Such a critical perspective is not unique to Ghana’s response to HIV/AIDS but serves as emblematic voice for similarly situated settings of the global south.