This study evaluates the cumulative multifactorial physical and chemical impacts resulting from coca production on amphibian populations in comparison with the potential impacts produced by the herbicide glyphosate (Glyphos), which, mixed with the surfactant Cosmo-Flux, is used in the spray control program for illicit crops in Colombia. Using similar worst-case assumptions for exposure, several other pesticides used for coca production, including mancozeb, lambda cyhalothrin, endosulfan, diazinon, malathion, and chlorpyrifos, were up to 10- to 100-fold more toxic to frogs than the Glyphos-Cosmo-Flux mixture. Comparing hazard quotients based on application rates, several of these compounds demonstrated hazards 3-383 times that of formulated glyphosate. Secondary effects, particularly of insecticides, are also a concern, as these agents selectively target the primary food source of amphibians, which may indirectly impact growth and development. Although the potential chemical impacts by other pesticides are considerable, physical activities associated with coca production, particularly deforestation of primary forests for new coca plots, portend the greatest hazard to amphibian populations. The entire production cycle of cocaine has been linked to ecosystem degradation. The clearing of pristine forests for coca propagation in Colombia is well documented, and some of these regions coincide with those that contain exceptional amphibian biodiversity. This is particularly problematic as coca production encroaches more deeply into more remote areas of tropical rain forest. Transportation of disease, including the chitrid fungus, to these remote regions via human intrusion may also adversely affect amphibian populations. Therefore, the cumulative impacts of coca production, through habitat destruction, application of agrochemicals, and potential transmission of disease, are judged to pose greater risks to amphibian populations in coca-growing regions than the glyphosate spray control program.