African trypanosomiases, including the human disease referred to as 'sleeping sickness' and the animal diseases such as nagana, surra and dourine, are neglected vector-borne diseases that after years of research still need improved diagnosis and chemotherapy. Advances in proteomics offer new tools to better understand host-vector-parasite crosstalks occurring during the complex parasitic developmental cycle, and to determine the outcome of both transmission and infection. Taken into account the contributions and pitfalls of using diverse proteomics tools argue about the interest of pathogenoproteomics, both to generate advances in basic research on the best knowledge and understanding of host-vector-pathogen molecular interactions, and to lead to the concrete development of new tools through the characterisation of key biomarkers to improve diagnosis and treatment management of trypanosomoses in the near future.