Significance Determining the drivers of extinction risk has been a key pursuit of conservation biology. Considering that body mass could be a strong predictor of extinction risk, we constructed a global database of body masses for 27,647 vertebrate species. Results show that the smallest- and largest-bodied vertebrates have elevated extinction risk. The largest vertebrates are mostly threatened by direct killing by humans, whereas the smallest species are more likely to have restricted geographic ranges—an important predictor of extinction risk—and be threatened by habitat degradation. Declines of large and small vertebrate species will truncate the size distributions characterizing these taxa, jeopardizing ecosystem services to humans, and generating cascading ecological and evolutionary effects on other species and processes.