Species that are Extinct in the Wild have succumbed to devastating threats that led to their extirpation from nature. Remaining only under human care in facilities like zoos and botanic gardens for up to 200 years, their fate hangs in the balance with recovery or extinction as possible outcomes. We review the state of Extinct in the Wild animal and plant populations and how these relate to past reintroduction attempts. The feasibility of future action depends upon the viability of ex situ populations as well as conditions in the wild. Overall, we demonstrate that vast and urgent effort is required to rescue more species from the wild, revitalize populations under human care, release species when appropriate, and reinforce created populations. We present a novel approach to evaluate and prioritize relative reintroduction potential by assessing the intactness of ecosystems within indigenous range. Irreversible threats from the past, or future threats like climate change, may render some indigenous ranges as unsuitable. We examine how national and global policy shifts facilitating responsible assisted colonization could help to yield new populations that may also serve as stepping-stones for the eventual return of species to former range. To prioritize cost-effective impacts, we present a novel approach of using the IUCN Green Status of Species to assess alternative benefits in concert with cost-share partnerships that can catalyze increased action for Extinct in the Wild and other species.