Due to its long-term isolation as an island continent, Australia’s mammal fauna is exceptional both for its evolutionary diversity and high endemism. It is the only place where representatives of the three surviving major mammal lineages coexist and is the only continent dominated by marsupials. Endemism is also high amongst the Australian rodent and microbat radiations. Over recent millennia and especially in the last 200 years, the trajectory of this unique mammal fauna has been one of decline and extinction, leaving the ecosystems of the continent profoundly altered. While much unique diversity been lost, increased scientific knowledge and growing management expertise has prevented many further extinctions. In such a dynamic and altered landscape, managing Australia’s unique mammals is a formidable challenge that includes encouraging the persistence of threatened species, as well as trying to suppressing introduced mammalian competitors and predators and some endemic species that are now over-abundant. While many threats to Australia’s mammals are ongoing and novel threats continue to arise, it is hoped that this unique fauna will persist and continue to fascinate.