The emergence of parasites resistant to anthelmintic macrocyclic lactones (MLs) threatens to severely limit current parasite control strategies. Improving the current ML-based chemotherapy to perpetuate the efficacy of this broad-spectrum class of anthelmintics would be advantageous. In recent years it has become evident that the absorption, distribution and elimination of the MLs in hosts and parasites are under the control of multidrug resistance transporters (MDRs) such as P-glycoproteins. Theoretically, the inhibition of these transporters should result in an increase of the drug concentration in the organisms and higher treatment efficiency. This opinion article will discuss the recent findings in this research field and assess the possibilities of this approach being used in the field.