The One Health approach has been once again highlighted during the covid-19 pandemic, notably with the One Health High-Level Experts Panel, created jointly by the Food and Agriculture Organization of the United Nations, the World Organisation for Animal Health, the United Nations Environment Programme (UNEP), and the World Health Organization (WHO). These organisations decided to mainstream One Health, to be better prepared for prevention, prediction, detection, and response to infectious diseases, all while considering interactions between humans, wildlife and domestic animals and ecosystems. We look at the history of the One Health approach, as defined in 2004, and show how Southeast Asia, a hotspot of the emergence of infectious diseases, played a leading role in the international adoption of this approach. We highlight how the region established the forerunner and the favourable elements of One Health. We finally present the tools and mechanisms of its implementation in the region and the evolution of its practices since OHHLEP’s creation.