Wildlife trade poses a major threat to biodiversity, yet the drivers determining which species are traded are not fully understood. Through a comprehensive collection of official and online trade data, we applied a binomial test to identify families that contain an unexpectedly large or small number of traded species. We also analyzed which factors predispose reptile species to be traded and explored whether traded species were more likely to be threatened with extinction. Of the 10,919 reptile species in our dataset, 3889 species (35.6%) were traded. There was strong evidence for taxonomic biases in trade risk. In particular, all turtle and crocodilian families had higher trade risk than other reptiles. Species with large body sizes, habitat generalists, insular endemics, and those found in regions with high gross domestic product were traded in greater quantities and more frequently. Species with small and large ranges were more frequently involved in trade, suggesting a demand for rare and common species in wildlife trade. When connecting trade risk to extinction risk, data-deficient and not-evaluated species had fewer traded species and were less likely to be traded than threatened or nonthreatened ones. Nonetheless, these species warrant special conservation attention considering their rarity, limited range size, and insufficient legal protection. Given the increased attention given to wildlife trade, we suggest implementing stronger regulatory measures to monitor and control the trade of reptile species, particularly those belonging to families with a high risk of being traded. Efforts should also prioritize the protection of species exhibiting traits that make them highly susceptible to exploitation. Finally, promoting international collaboration for stricter enforcement of wildlife trade regulations and support of sustainable trade practices can help mitigate the negative impacts on biodiversity.