The article aims to reflect on the importance of implementing risk management for the conservation of diverse collections in different contexts. The discussion is based on the experience of teams at the Oswaldo Cruz Foundation in Rio de Janeiro, Brazil, a century-old institution devoted to research and development in public health and that has various types of historical and scientific collections in its custody. From 2014 to 2018, Casa de Oswaldo Cruz, the unit in charge of the foundation’s heritage, conducted a pilot experience in the implementation of risk management for the Fiocruz collections, adopting the ABC Method developed by the International Centre for the Study of the Preservation and Restoration of Cultural Property (ICCROM) and the Canadian Conservation Institute (CCI). The result of this pilot experience was essential for expanding knowledge of the different risks that can impact the foundation’s cultural heritage and for proposing mitigation measures. The COVID-19 pandemic brought new challenges for the institution and required rethinking strategies to guarantee the safety and security of collections, employees, and users, considering contextual changes that included alterations in the uses of the sites where the collections are located and the ways of accessing them.