In recent years it has become clear that membrane transport proteins are overrepresented as drug targets and resistance determinants in the most virulent malaria parasite, Plasmodium falciparum. One important new drug target is PfATP4, a P-type ATPase located on the parasite plasma membrane that is believed to extrude Na+ from the parasite while importing H+. Numerous chemically diverse compounds target PfATP4 and several of these have been tested in humans, with the spiroindolone cipargamin poised to become the first PfATP4 inhibitor to reach the field. We will present our data showing that P. falciparum parasites can acquire a G358S mutation in PfATP4 that confers them with a clinically significant level of resistance to cipargamin and certain other PfATP4 inhibitors. The mechanism by which the G358S mutation confers resistance, and the consequence of the mutation for parasite fitness and physiology, will be presented. Several P. falciparum transporters that are yet to be characterised have also been implicated in parasite resistance to antimalarial lead compounds recently. We have generated P. falciparum parasites in which the expression levels of these transporters are increased or can be reduced in an inducible manner, and will present our findings on the roles of these transporters in modulating parasite response to antimalarial candidates.