It is worldwide recognized that the use of pharmaceuticals for human and veterinary purposes could lead to unsustainable effects on the environment. A strategy to reduce the impact of pharmaceuticals on the environment has been recently established at European level, where guidelines to evaluate the impacts of veterinary drugs used to treat animal diseases are in place. The aim of this article is to focus on the worldwide used antiparasitic drug ivermectin (IVM) and its potential impact on the environment. A specific section is related to the IVM resistance that the massive use of this drug could generate enhancing the risk scenarios also for human health. The application of stringent measures for the veterinary use of this substance, in line with the recommendations provided by International frameworks such as One Health and EcoHealth, is recommended.