Anemonefishes share a number of life history and ecological traits, and some unfortunate links to human-induced stress, that expose some of the 28 species to the risk of extinction. The biodiversity hotspot for anemonefishes extends across Southeast Asia to the western Pacific, including many countries where there are high levels of human impact and few effective management strategies. Anemonefish biodiversity is threatened by anemone bleaching, direct effects of ocean warming and acidification, collection for the aquarium trade, and coastal development. These risks are exacerbated by extreme habitat specialization, the mutual anemonefish–anemone relationship, low abundance, low population connectivity, small geographic ranges, and shallow depth ranges. Many species exhibit two or three of these traits, with small range species often associated with fewer anemone hosts and narrower depth ranges, exposing them to double or triple jeopardy. While all species have not been assessed by the IUCN, our detailed analysis of area of occupancy indicates that three species are extremely close to the threshold for being classified as Critically Endangered. Marine reserves have been effective in protecting species from exploitation and helping sustain marginal populations across generations, but effective population sizes are often very small and recovery can be slow. Additional management efforts need to focus on sustainable collecting practices and the protection and restoration of critical anemone habitats.