The prospect of extinction, the complete loss of a species or other group of organisms, has long provoked strong responses. Until the turn of the 18th century, deeply held and widely shared beliefs about the order of nature led to a firm rejection of the possibility that species could entirely vanish. During the 19th century, however, resistance to the idea of extinction gave way to widespread acceptance following the discovery of the fossil remains of numerous previously unknown forms and direct experience with contemporary human-driven decline and the destruction of several species. In an effort to stem continued loss, at the turn of the 19th century, naturalists, conservationists, and sportsmen developed arguments for preventing extinction, created wildlife conservation organizations, lobbied for early protective laws and treaties, pushed for the first government-sponsored parks and refuges, and experimented with captive breeding. In the first half of the 20th century, scientists began systematically gathering more data about the problem through global inventories of endangered species and the first life-history and ecological studies of those species. The second half of the 20th and the beginning of the 21st centuries have been characterized both by accelerating threats to the world’s biota and greater attention to the problem of extinction. Powerful new laws, like the U.S. Endangered Species Act of 1973, have been enacted and numerous international agreements negotiated in an attempt to address the issue. Despite considerable effort, scientists remain fearful that the current rate of species loss is similar to that experienced during the five great mass extinction events identified in the fossil record, leading to declarations that the world is facing a biodiversity crisis. Responding to this crisis, often referred to as the sixth extinction, scientists have launched a new interdisciplinary, mission-oriented discipline, conservation biology, that seeks not just to understand but also to reverse biota loss. Scientists and conservationists have also developed controversial new approaches to the growing problem of extinction: rewilding, which involves establishing expansive core reserves that are connected with migratory corridors and that include populations of apex predators, and de-extinction, which uses genetic engineering techniques in a bid to resurrect lost species. Even with the development of new knowledge and new tools that seek to reverse large-scale species decline, a new and particularly imposing danger, climate change, looms on the horizon, threatening to undermine those efforts.