Significance Despite growing evidence of the deleterious effects on ecological and human health, little is known regarding the global occurrence of pharmaceuticals in rivers. Studies assessing their occurrence are available for 75 of 196 countries, with most research conducted in North America and Western Europe. This leaves large geographical regions relatively unstudied. Here, we present the findings of a global reconnaissance of pharmaceutical pollution in rivers. The study monitored 1,052 sampling sites along 258 rivers in 104 countries of all continents, thus representing the pharmaceutical fingerprint of 471.4 million people. We show that the presence of these contaminants in surface water poses a threat to environmental and/or human health in more than a quarter of the studied locations globally.