Beginning with the emergence fifty years ago of Plasmodium falciparum parasites that are resistant to chloroquine (CQ), efforts to control malaria have been thwarted by failed or failing drugs. Mutations in one protein, the ‘CQ resistance transporter’ (PfCRT), are the primary cause of CQ resistance in the parasite. These mutations result in a marked reduction in the accumulation of CQ at its site of action in the parasite’s digestive vacuole. Mutations in PfCRT also cause increases or decreases in the parasite’s sensitivity to a number of other antimalarial drugs. My lab has established a novel and robust system for the study of PfCRT in Xenopus laevis oocytes. Using this system we have shown that a resistance-conferring form of the protein has the ability to transport CQ out of the digestive vacuole whereas the wild-type protein does not (Martin et al. Science 2009; 325: 1680-82). CQ-resistant strains possess between four and ten mutations in PfCRT; however the reason for this variation is not clear, nor is it known how many mutations are required to confer CQ transport activity upon PfCRT. An in-depth characterisation of the transport activities of a broad range of PfCRT variants, and the clinical implications of this work, will be presented.