This chapter explores the political economy of African trypanosomiasis knowledge and policy in Zambia. Trypanosomiasis is transmitted by tsetse flies of the genus Glossina and its distribution consequently reflects that of its vector. Human African trypanosomiasis (HAT) can be a fatal disease and African animal trypanosomiasis (AAT) can also be fatal in all livestock species, but commonly causes chronic debilitating disease and loss of production. The focal distribution of trypanosomiasis can have great socio-economic effects. A significant proportion of HAT patients are active adults, often because their work brings them into contact with tsetse. Wildlife constitutes an important trypanosomiasis reservoir in Zambia, with most host species capable of supporting asymptomatic infections due to co-evolution over many centuries. Stakeholders held very different views on trypanosomiasis, which was found to be at the heart of the different disease narratives circulating in Zambia.