Human African trypanosomiasis (HAT), or sleeping sickness, is a parasitic infection that is almost invariably fatal unless treated. It is a neglected tropical disease that occurs in sub-Saharan Africa. The incidence of the disease is declining in response to intensive surveillance and control in endemic areas. As a result, HAT is among the neglected tropical diseases targeted by the World Health Organization (WHO) for elimination. WHO maintains exhaustive records of all declared cases; in 2018, a historically low number of cases (less than 1000) was reported. The remarkable progress in the control of gambiense HAT has relied on case-finding and curative treatment, a strategy that interrupts transmission by depleting the reservoir of parasites in humans. This has been combined occasionally with vector control activities. The subject of these guidelines, therefore, is of utmost importance for the continuation of progress to eliminate HAT. The recent approval of a new medicine (fexinidazole) for the treatment of gambiense HAT has opened new possibilities for the management of cases and thus warrants the new WHO recommendations contained herein. While studies of fexinidazole and other therapies are ongoing, these guidelines are considered interim guidelines until new information becomes available. This document focuses on the management of patients affected by gambiense HAT and constitutes an update to the WHO therapeutic guidance issued in 2013.