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High numbers of threatened species might be expected to occur where overall species richness is also high; however, this explains only a proportion of the global variation in threatened species richness. Understanding why many areas have more or fewer threatened species than would be expected given their species richness, and whether that is consistent across taxa, is essential for identifying global conservation priorities. Here, we show that, after controlling for species richness, environmental factors, such as temperature and insularity, are typically more important than human impacts for explaining spatial variation in global threatened species richness. Human impacts, nevertheless, have an important role, with relationships varying between vertebrate groups and zoogeographic regions. Understanding this variation provides a framework for establishing global conservation priorities, identifying those regions where species are inherently more vulnerable to the effects of threatening human processes, and forecasting how threatened species might be distributed in a changing world. Understanding to what extent geographic patterns in threatened species diversity are driven by environmental features or human activities could aid conservation. Here, Howard et al. investigate broad scale patterns in species richness of threatened vertebrates and test the role of environmental and anthropogenic drivers.