Some of the most isolated islands in the Pacific Ocean are home to US National Parks and Wildlife Refuges. These islands are known for flora and fauna that occur nowhere else, but also for invasive species and other factors which have resulted in the disproportionate extinction of native species. The control of invasive mammals is the single most expensive natural resource management activity essential for restoring ecological integrity to parks in the Hawaiian Islands, American Samoa, and the islands of Guam and Saipan. Science-based applications supporting management efforts have been shaped by longstanding collaborative federal research programs over the past four decades. Consequently, feral goats (Capra hircus) have been removed from >690 km2 in National Parks, and feral pigs (Sus scrofa) have been removed from >367 km2 of federal lands of Hawai‘i, bringing about the gradual recovery of forest ecosystems. The exclusion of other non-native ungulates and invasive mammals is now being undertaken with more sophisticated control techniques and fences. New fence designs are now capable of excluding feral cats (Felis catus) from large areas to protect endangered native waterfowl and nesting seabirds. Rodenticides which have been tested and registered for hand and aerial broadcast in Hawai‘i have been used to eradicate rats from small offshore islands to protect nesting seabirds and are now being applied to montane environments of larger islands to protect forest birds. Forward-looking infrared radar (FLIR) is also being applied to locate wild ungulates which were more recently introduced to some islands. All invasive mammals have been eradicated from some remote small islands, and it may soon be possible to manage areas on larger islands to be free of invasive mammals at least during seasonally important periods for native species.