This article uses fieldwork conducted among North American and Ugandan HIV researchers to track the evolution of molecular HIV science in the global context. The recent initiation of programs funding free antiretroviral treatment in sub-Saharan Africa has both forestalled the deaths of millions of patients and brought molecular medicine to the continent on a massive scale. However, in the years leading up to this development, scientists and policymakers engaged in heated debates over whether HIV treatment in Africa could succeed, with many arguing that economic and ‘cultural’ factors would lead to missed pills and the rapid development of drug-resistant HIV strains. This article describes how the molecular ‘maps’ upon which knowledge claims about HIV were made (including claims about treatment and drug resistance) are based on HIV strains found primarily in patients in North America and Europe, and raises questions about what this implies for patients and scientists in Africa and other regions in the global South. Borrowing from the insights of critical geographers, I argue that our genetic maps of HIV are partial and contingent and reflect a ‘molecular politics’ in which the global inequalities of the AIDS epidemic are manifest at the most minute scale, embedded within the very materials and tools scientists use to study HIV. The consequences of this fact are at once clinical, political and epistemological.