The endemic Galapagos Damselfish, Azurina eupalama, has not been seen since the historically large El Niño Southern Oscillation (ENSO) of 1982/3. Many observers and expeditions have attempted to find the species in the more than 4 decades since, but without success. Prior to 1982, the species had been regularly observed and numerous specimens were collected by almost all historical collecting expeditions conducted since the species was discovered in 1898. During ENSO events, the cessation of cold upwelling and high plankton productivity typical of normal years results in sustained periods of exceptionally warm water, reducing populations of cool-water fishes and severely affecting many other marine and terrestrial organisms. The Galapagos Damselfish was an obligate planktivore, limited to the exposed shallow shorelines of the islands of the Galapagos, and adapted to cooler sea-surface temperatures, and thus especially vulnerable to extinction due to climate change. The species, presently classified by the IUCN Red List as critically endangered/possibly extinct, should now be considered likely extinct. Future searches by sampling environmental DNA from Galapagos waters may be able to further confirm this tragic outcome of human-induced global climate change on this fragile and uniquely iconic world heritage site.