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Funding for species conservation is insufficient to meet the current challenges facing global biodiversity, yet many programs use expensive single-species recovery actions and neglect broader management that addresses threatening processes. Arid Australia has the world's worst modern mammalian extinction record, largely attributable to competition from introduced herbivores, particularly European rabbits (Oryctolagus cuniculus) and predation by feral cats (Felis catus) and foxes (Vulpes vulpes). The biological control agent rabbit hemorrhagic disease virus (RHDV) was introduced to Australia in 1995 and resulted in dramatic, widespread rabbit suppression. We compared the area of occupancy and extent of occurrence of 4 extant species of small mammals before and after RHDV outbreak, relative to rainfall, sampling effort, and rabbit and predator populations. Despite low rainfall during the first 14 years after RHDV, 2 native rodents listed by the International Union for Conservation of Nature (IUCN), the dusky hopping-mouse (Notomys fuscus) and plains mouse (Pseudomys australis), increased their extent of occurrence by 241-365%. A threatened marsupial micropredator, the crest-tailed mulgara (Dasycercus cristicauda), underwent a 70-fold increase in extent of occurrence and a 20-fold increase in area of occupancy. Both bottom-up and top-down trophic effects were attributed to RHDV, namely decreased competition for food resources and declines in rabbit-dependent predators. Based on these sustained increases, these 3 previously threatened species now qualify for threat-category downgrading on the IUCN Red List. These recoveries are on a scale rarely documented in mammals and give impetus to programs aimed at targeted use of RHDV in Australia, rather than simply employing top-down threat-based management of arid ecosystems. Conservation programs that take big-picture approaches to addressing threatening processes over large spatial scales should be prioritized to maximize return from scarce conservation funding. Further, these should be coupled with long-term ecological monitoring, a critical tool in detecting and understanding complex ecosystem change.