Gastro-intestinal nematode infections are highly prevalent in herbivores worldwide and cause serious economical losses in ruminant breeding. Up to 11 classes of anthelmintic drugs exist to control gastro-intestinal nematode infections. Each class of anthelmintic drugs is characterized by a specific mode of action although multidrug resistance mechanisms may be involved. Two main groups can be defined according to their action on membrane ion channels, or on their biochemical action on enzyme inhibition. Anthelmintic resistance has been recorded extensively for only 3 or 4 classes of anthelmintic drugs, namely, benzimidazoles, macrocyclic lactones and tetrahydropyrimidines or levamisole. These anthelmintic drugs classes are efficient against gastro-intestinal and pulmonary nematodes and represent the main portion of anthelmintic drugs used in the world. Newly developed drugs include monepantel and derquantel Despite a remarkably diverse choice of anthelmintic drugs, gastro-intestinal nematode infections are poorly controlled in the field. Anthelmintic resistance has become so frequent worldwide that even if anthelmintic drug classes act in a different manner on nematode biology, it is unlikely they can reverse the increasing reports of multi-resistant populations of nematodes. Mathematical models have been elaborated to address the importance of genetic mechanisms (monogenic or multigenic) and to evaluate the sustainability of breeding management systems (number of treatment, management of pastures...). This theoretical approach allows for the simulation, in silico, of very low initial resistance allelic frequencies and over successive years which is not tractable via experimentations. In this chapter, we propose an exhaustive presentation of the available classes of anthelmintic drugs, their mode of action, and if known, the identified drug resistance mechanisms (benzimidazoles), or putative ones (macrocyclic lactones, tetrahydropyrimidines, levamisole). After a presentation of factors associated with the increase in anthelmintic resistance, the available strategies to slow down the development of anthelmintic drugs resistance such as: Targeted Selective Treatment (TST), Targeted-Treatment (TT), and the use of drug combinations (combos) will be evaluated. We also discuss the agricultural practices implemented to control the dynamics of gastro-intestinal nematode infections in field conditions. Management of nematode infection and resistance against anthelmintics: Towards a sustainable control in herbivores.