This paper traces the development of policies dealing with HIV/AIDS in Botswana from their beginning in the late 1980s to the current programme to provide population-wide anti-retroviral therapy (ARV). Using a variety of source material, including long-term ethnographic research, it seeks to account for the failure of Western-inspired approaches in dealing with the pandemic. It does this by looking at the cultural and institutional features that have created resistance to the message and inhibited effective implementation. The negative response to the first educational campaign stressing condom use is described and contextualized in terms of Tswana ideas of morality and illness. Nor, as was initially expected, did the introduction of free ARV therapy operate to break the silence and stigma that had developed around the disease. Take-up was very slow, and did not operate to encourage widespread testing. In 2003, key policymakers in Botswana began to argue for a break with the AIDS ‘exceptionalism’ position, with its emphasis on voluntarism, confidentiality and the human rights of patients. This resulted in routine testing being introduced in 2004. This links to a major argument running through the paper which is that the failure of policy cannot be attributed solely to the nature of local populations. Western cultural assumptions about ‘good practice’ also require critical examination.