Elimination programs targeting TriTryp diseases (Leishmaniasis, Chagas' disease, human African trypanosomiasis) significantly reduced the number of cases. Continued surveillance is crucial to sustain this progress, but parasite molecular surveillance by genotyping is currently lacking. We explain here which epidemiological questions of public health and clinical relevance could be answered by means of molecular surveillance. Whole-genome sequencing (WGS) for molecular surveillance will be an important added value, where we advocate that preference should be given to direct sequencing of the parasite's genome in host tissues instead of analysis of cultivated isolates. The main challenges here, and recent technological advances, are discussed. We conclude with a series of recommendations for implementing whole-genome sequencing for molecular surveillance.