The 4-aminoquinolines, including chloroquine and amodiaquine, and the quinolinemethanols, including quinine and mefloquine, concentrate inside the acidic digestive vacuole, where they are believed to bind β-hematin and interfere with heme detoxification. The falcipain inhibitors that are under development target cysteine proteases that participate in hemoglobin degradation in this digestive vacuole. Antibiotics such as azithromycin, doxycycline, and clindamycin act inside the chloroplast-like plastid organelle, where they inhibit protein translation, resulting in the death of the progeny of drug-treated parasites (the “delayed-death” phenotype). Atovaquone and select other compounds inhibit electron transport in the mitochondrion, whereas antifolates disrupt de novo biosynthesis of folate in the cytosol. Only drugs for which the site of action is known with confidence are assigned to a subcellular location. Indeed, the targets and sites of action of other antimalarials, including artemisinin and artemisin derivatives, remain an area of active investigation. Reproduced with permission from Nature Publishing Group (44).