Extinctions are occurring at an unprecedented rate as a consequence of human activities. Vertebrates constitute the best-known group of animals, and thus the group for which there are more accurate estimates of extinctions. Among them, freshwater fishes are particularly threatened and many species are declining. Here we report the extinction of an endemic freshwater fish of Mexico, the Catarina pupfish Megupsilon aporus, the sole species of the genus Megupsilon. We present a synopsis of the discovery and description of the species, the threats to, and degradation of, its habitat, and the efforts to maintain the species in captivity before it became extinct in . The loss of the Catarina pupfish has evolutionary and ecological implications, and highlights the crisis of freshwater fish extinctions. It is a warning of the likely fate of more than  freshwater fish species threatened with extinction in Mexico. To save these species, the country urgently needs a national strategy to articulate a bold conservation effort, with better policies on ecosystem management and water use.