The One Health concept initiated at the beginning of the century as the “One World One Health” initiative, has many roots historically and has been given plenty of definitions and populates a constellation of related concepts (ecohealth, planetary health, global health, environmental health, etc.). It has gained momentum with the increasing frequency of disease emergence and pandemics and the failure of traditional public health approach and biosecurity to prevent them. This had led WHO, WOAH, FAO and UNEP to jointly propose a “new definition (of One Health) for a sustainable and healthy future” (OHHLEP et al., 2022). However, there is still a long road ahead to fully integrate the multiple disciplines and concepts, to organize governance making their implementation possible in the field, and to subsequently mobilize sufficient manpower and appropriate funding (Destoumieux-Garzón et al., 2018; Giraudoux et al., 2022). Here we discuss the challenges posed by the increasing emergence of human, animal and ecosystem health issues and how a nexus approach of those issues is necessary (see IPBES (2020) and ongoing nexus assessment 2022-2024, IPBES (2019)). This applies to a large number of human health issues in the African Great Rift, those known (e.g. Ebola disease, Monkeypox, Malarias, Cholera, Echinococcoses, etc.) as well as those still unknown and incubating, whose origin and expansion combine with the deterioration of local socioecosystems. Destoumieux-Garzón, D., Mavingui, P., Boetsch, G., Boissier, J., Darriet, F., Duboz, P., Fritsch, C., Giraudoux, P., Le Roux, F., Morand, S., Paillard, C., Pontier, D., Sueur, C., Voituron, Y., 2018. The One Health Concept: 10 Years Old and a Long Road Ahead. Front. Vet. Sci. 5. https://doi.org/10.3389/fvets.2018.00014 Giraudoux, P., Besombes, C., Bompangue, D., Guégan, J.-F., Mauny, F., Morand, S., 2022. One Health or One Health washing: an alternative more than ever to overcome. CABI One Health 1–4. https://doi.org/10.1079/cabionehealth20220006 IPBES, 2020. Workshop Report on Biodiversity and Pandemics of the Intergovernmental Platform on Biodiversity and Ecosystem Services. IPBES, Bonn, Germany. https://doi.org/10.5281/zenodo.4147317 IPBES, 2019. Nexus assessment [WWW Document]. IPBES Secr. URL https://ipbes.net/node/35931 (accessed 9.15.22). OHHLEP, Adisasmito, W.B., Almuhairi, S., Behravesh, C.B., Bilivogui, P., Bukachi, S.A., Casas, N., Becerra, N.C., Charron, D.F., Chaudhary, A., Zanella, J.R.C., Cunningham, A.A., Dar, O., Debnath, N., Dungu, B., Farag, E., Gao, G.F., Hayman, D.T.S., Khaitsa, M., Koopmans, M.P.G., Machalaba, C., Mackenzie, J.S., Markotter, W., Mettenleiter, T.C., Morand, S., Smolenskiy, V., Zhou, L., 2022. One Health: A new definition for a sustainable and healthy future. PLOS Pathog. 18, e1010537. https://doi.org/10.1371/journal.ppat.1010537