The pressure on health donors and aid-dependent governments to reach the end of AIDS has been managed in part through the rising dominance of discourses and tools grounded in cost-effectiveness. This chapter analyzes cost-effectiveness tools used to prioritize HIV financing at the national level, and finds that the tools can be a double-edged sword for marginalized communities and interventions. While cost-effectiveness analysis can be used to make a case for prioritizing investment in HIV services that reach key populations, these tools can also be used to reinforce epistemological exclusion of those populations due to lack of quantitative data that demonstrates their needs. Cost-effectiveness is sometimes also used to exclude other values, principles, and knowledge produced through qualitative methods. This chapter examines how cost-effectiveness analyses play out for key populations in some national investment cases, and explores whether human rights norms offer alternative principles of decision-making. It finds that while cost-effectiveness analysis can contribute towards ensuring that states fulfill the right to health, if not explicitly balanced against other human rights principles, cost-effectiveness may reinforce neoliberal values and a model of the market in which small, marginalized populations are set up to lose the competition for prioritization.