Amphibian population declines far exceed those of other vertebrate groups, with 30% of all species listed as threatened by the International Union for Conservation of Nature1,2,3. The causes of these declines are a matter of continued research, but probably include climate change, land-use change and spread of the pathogenic fungal disease chytridiomycosis1,4,5. Here we assess the spatial distribution and interactions of these primary threats in relation to the global distribution of amphibian species. We show that the greatest proportions of species negatively affected by climate change are projected to be found in Africa, parts of northern South America and the Andes. Regions with the highest projected impact of land-use and climate change coincide, but there is little spatial overlap with regions highly threatened by the fungal disease. Overall, the areas harbouring the richest amphibian faunas are disproportionately more affected by one or multiple threat factors than areas with low richness. Amphibian declines are likely to accelerate in the twenty-first century, because multiple drivers of extinction could jeopardize their populations more than previous, mono-causal, assessments have suggested.