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Heavy deforestation and land use conversion in Southeast Asia caused most of the mammals to face the threat of extinction due to limited availability of suitable habitats, which jeopardizes their survival throughout the region. As the demand for certain body parts of threatened mammals increases, illegal poaching activities increase, and consequently their population continuously decreases. Protecting sustainable population numbers or supporting efforts to multiply the population of threatened mammals in their own natural habitats is very challenging, almost impossible until the threats in the wild are removed. Therefore, ex-situ conservation through captive breeding is another reliable method which already been practiced for years across the world. Nevertheless, transferring and raising these mammals in breeding centers requires proper guidelines to maintain their welfare and genetic variability. In this paper, we discussed threatened mammals native to Southeast Asian countries that are currently under captive breeding programs. A multi-disciplinary overview, including: group size and social structure; health, stress and mortality studies and; enclosure design and environmental enrichment, are key components of the best management and husbandry practices. The mammalian alleles may experience evolutionary change if the populations of endangered mammals are retained in captivity after few generations, and that could lead to genetic problems. Therefore, a proper gene ‘flow’ is crucial to maintain genetic variation within and between populations. Finally, an important tool for species conservation is reintroduction of well-managed captive breeding populations into the wild. A complete health screening, selection of sites and pre-release training prior to reintroduction are crucial and need to be addressed for these mammalian populations.