Wildlife trade is a multibillion dollar industry that is driving species toward extinction. Of >31,500 terrestrial bird, mammal, amphibian, and squamate reptile species, similar to 18% (N = 5579) are traded globally. Trade is strongly phylogenetically conserved, and the hotspots of this trade are concentrated in the biologically diverse tropics. Using different assessment approaches, we predict that, owing to their phylogenetic replacement and trait similarity to currently traded species, future trade will affect up to 3196 additional species-totaling 8775 species at risk of extinction from trade. Our assessment underscores the need for a strategic plan to combat trade with policies that are proactive rather than reactive, which is especially important because species can quickly transition from being safe to being endangered as humans continue to harvest and trade across the tree of life.