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Chile is a country with a unique and diverse geography, making it a “natural laboratory” for important scientific disciplines, like astronomy and glaciology. Frequently, this potential has benefited foreign research institutions the most. However, in the case of disaster research, the Chilean scientific community and the government have worked together to develop a national research agenda in order to make the country more resilient, but also, to position Chile as a leader in terms of research, development and innovation (R&D+i) related to disaster risk and its major components (hazards, exposure, vulnerability and capacity). The implementation of this strategy demands a total investment of $914 million USD in 20 years, which is expected to have a benefit-cost ratio of 2.32, and annual savings of about $106 million USD. This article describes the efforts made in this direction since 2016, starting with the creation of a commission involving experts from the academia, public and private sectors, NGOs and the armed forces to define a R&D+i strategy, and following the development of the newly created National Technological Institute for Disaster Resilience (ITReND). The focus of this paper is on exploring the major challenges and lessons of the Chilean case, trying to explain its central position as an actor in this area of research, considering its location in the periphery of the world. Finally, the possibility of generating new scientific and technological hubs in the “Global South” that transcend the model of the “natural laboratory” will also be discussed