This document focuses on the management of patients affected by gambiense HAT and constitutes an update to the WHO therapeutic guidance issued in 2013. The main changes in recommendations concern the criteria and methods for deciding the treatment among the new set of therapeutic options and the particular conditions that apply to treatment with fexinidazole, as outlined below. Because HAT is a serious, life-threatening disease and because the efficacy of fexinidazole depends on swallowing the medicine after an appropriate intake of food as well as on completing the full 10-day treatment schedule, the recommendations regarding fexinidazole administration are considered key elements that must be carefully followed. When the conditions listed in these guidelines are not met for any individual patient, the alternative available treatments should be prescribed.