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Malaria is a major global health concern, with half of the world鈥檚 population being at risk of infection.Among the Plasmodium species that infect humans, P. falciparum causes most fatalities. Chloroquine (CQ) was the drug of choice for decades and considered safe, affordable and easy-to-use until resistance emerged. To date, no other antimalarial drug has been able to avoid emergence of resistance as long as chloroquine. However, the exact mechanism of CQ resistance is still not known. As resistance is starting to emerge for the currently used artemisinin-based combination therapies only a few years after their introduction, it is of high importance to understand the mechanism of resistance to drugs such as chloroquine. CQ is suggested to accumulate in the parasite鈥檚 digestive vacuole due to its weak base properties, where it unfolds its antimalarial action.