Creating predator-free islands is a cost-effective strategy in the long-term to reduce their impact on island fauna. Large, inhabited islands are frontiers for eradication programs as these pose logistical as well as socio-political challenges, but offer great potential benefits. A long-term program to eradicate red foxes (Vulpes vulpes) was initiated on Phillip Island, Victoria, Australia, to eliminate their impact on ground-nesting birds, particularly little penguins (Eudyptula minor). The fox population on this 100 km² permanently inhabited island has been reduced to undetectable levels. A Bayesian catch-effort model has been developed to assess fox population size, the effectiveness of the multiple detection methods that have been deployed, and the probability of eradication. With the success of the fox control program, a threatened species translocation program has been initiated: Phillip Island Ark. This program has begun with a successful trial introduction on Churchill Island, near Phillip Island, of the eastern barred bandicoot (Perameles gunnii), a species listed in Victoria as ‘extinct in the wild’. Future translocations are being planned to return other species that have either been lost on Phillip Island or are threatened species that cannot persist in the presence of invasive predators such as red foxes. Translocation programs such as this capitalise on our ability to effectively manage invasive predators on large inhabited islands. We present common management principles and lessons learned that can guide other pest eradication attempts and ultimately save threatened species from extinction.