The control of ruminant gastrointestinal nematodes and ectoparasites, one of the major production health problems, are heavily reliant on the systematic and sometimes abusive use of anthelmintic drugs. Endectocides are the most frequently used drugs, having high potency against arthropods and nematodes. Their dung pat residues enhance the risk of adverse effects on non-target invertebrates and on the general grazing cattle ecosystem. In this scenario, our objective is to review current knowledge of the agro-environmental and biodiversity impact and risks of endectocides in South America. The effects of faecal drug residues of ivermectin and doramectin on dung colonising invertebrates and dung degradation have been reported in studies carried out in the temperate centre of Argentina and in the subtropical region of Brazil. The results from Argentina showed a depression in invertebrate colonisation and degradation of dung recovered from endectocide treated cattle during the autumn. Comparisons have shown that ivermectin and doramectin have similar adverse effects. A decrease of Coleoptera larvae, Diptera larvae, Staphylinidae, Collembola, Acari and dung specific nematodes was noted in pats from both endectocides. The results from Brazil showed that dipterous larvae, Polyphaga coleopteran larvae and adults and mites were significantly reduced in the ivermectin treated group. The disturbances that macrocyclic lactones can produce on non-targeted invertebrates and on their associated participation in dung degradation and soil element recycling, are unpredictable and can negatively influence biodiversity and the agricultural ecosystem sustainability.