Abstract: Since the 1950s, intensive human activities such as reclamation and dam construction (for flood control, irrigation, and hydropower etc.) have caused serious fragmentation of the Yangtze biogeographic unit, greatly altering its pattern and processes, and accelerated by overfishing, many species especially the flagship dolphin and sturgeons have been seriously threatened and even extinct. This review aims to discuss the rescue of endangered species in the Yangtze River from an appoint view of conservation biogeography. It gives an introduction to the origin and evolution of the Yangtze biogeographic unit, describes government conservation initiatives, and discusses the challenges in protecting the endangered species. It is needed to explore how to repair the integrity of the Yangtze biogeographic unit or how to re-naturalize it based on the new paradigm of conservation biogeography, so as to being capable of rescuing endangered species, ultimately achieving harmonious coexistence between humans and nature.