Antiparasitic macrolides (or endectocides) represent the most recent class of antiparasitic drugs. This class is homogeneous because of its unique and specific, glutaminergic, mode of action, and its pharmacological properties. These drugs have a spectrum of action directed against many nematodes, as well as many insects and mites. Their structures and associated galenic formulations also enable them to have a high remanent potential. Unfortunately, endectocides are generally used in African countries without any recording procedure. Moreover, the introduction of generic formulations facilitated massive and repetitive uses that have led to therapeutic failures. These drugs should be given a good set-up to be effective in an African tropical environment, in particular by taking into account the characteristics of local breeds and environmental constraints. The first element to consider is the choice of the most potent route of administration. At the same time, the differences observed between animal species targets as well as physiological peculiarities must lead to a better adapted use.