Pythons are harvested for the international leather industry and pet trade. We analyzed the CITES export records (1999–2008) of the most intensively commercialized wild pythons (Python regius,Python sebae,Python reticulatus,Python molurus,Python curtus species complex) from African and Asian countries where reliable data on trade rates and ecology are available. Mean declared annual numbers of exported pythons were 30,000 in five African countries and 164,000 in Indonesia. Trade intensity tripled in Indonesia over the last decade, but declined in Africa. African international trade is exclusively associated with the pet market (mainly United States and Europe), whereas Asian pythons are sold mostly for luxury leather, albeit more recently also for the pet trade. A negative correlation between the annual numbers of pythons traded in Africa vs. Asia suggests a rapid and recent shift of the pressure exerted on wild populations in the two main exporting continents. We also found a strong effect of the currency exchange rate (i.e., U.S.$/€, the currencies used by the major importing countries) on African python exports: when the cost per African python increased, importers relied increasingly on Asian providers for pet trade. Overall, our data indicate that Asian pythons (especially P. reticulatus) might be threatened due to the rapidly increasing pressure, whereas the decreasing international trade in African pythons is likely more sustainable.