▪ Abstract The accidental introduction of the brown treesnake (Boiga irregularis) on Guam around 1950 induced a cascade of extirpations that may be unprecedented among historical extinction events in taxonomic scope and severity. Birds, bats, and reptiles were affected, and by 1990 most forested areas on Guam retained only three native vertebrates, all of which were small lizards. Of the hypotheses to account for the severity of this extinction event, we find some support for the importance of lack of coevolution between introduced predator and prey, availability of alternate prey, extraordinary predatory capabilities of the snake, and vulnerabilities of the Guam ecosystem. In addition, there were important interactions among these factors, especially the presence of introduced prey (possessing coevolutionary experience) that were thus able to maintain their populations and provide alternate prey to the introduced predator while it was driving the native prey species to extinction. This complex of vulnerabilities is common on oceanic islands.