Treatment of second-stage gambiense human African trypanosomiasis relied on toxicarsenic-based derivatives for over 50 years. The availability and subsequent use of eflornithine,initially in monotherapy and more recently in combination with nifurtimox (NECT), has drasticallyimproved the prognosis of treated patients. However, NECT logistic and nursing requirementsremain obstacles to its deployment and use in peripheral health structures in rural sub-SaharanAfrica. Two oral compounds, fexinidazole and SCYX-7158, are currently in clinical development.The main scope of this article is to discuss the potential impact of new oral therapies to improvediagnosis-treatment algorithms and patients’access to treatment, and to contribute to reach theobjectives of the recently launched gambiense humanAfrican trypanosomiasis elimination program