Several parasite proteins have been implicated in decreased susceptibility to artemisinins (ARTs), including PfATP6 (proposed to be in the endoplasmic reticulum [41]), PfMDR1 on the digestive vacuole [42], PfMRP1 on the parasite plasma membrane [43], and UBP-1 whose ortholog in Plasmodium chabaudi is associated with ART resistance [44]. The digestive vacuole protein PfCRT is also indicated as mutations that confer chloroquine resistance have been shown to significantly increase susceptibility to ARTs [45]. Host hemoglobin is delivered via cytostomes to the digestive vacuole, wherein it is proteolytically degraded. This liberates iron-heme (Fe-protoporphyrin IX) moieties, with subsequent oxidation of iron. Iron-heme is detoxified via its incorporation into hemozoin crystals. Iron-heme is thought to activate ARTs via interaction with the endoperoxide bridge, with the resulting ART radicals causing cellular damage [46 •• ]. Investigations of field isolates and drug-pressured laboratory lines have implicated quiescence or dormancy of early ring-stage parasites in resistance to ART action [47 • –49 • ]. ART, artemisinin; AP, apicoplast; Cs, cytostome; DV, digestive vacuole; ER, endoplasmic reticulum; Hb, hemoglobin; Hz, hemozoin; MT, mitochondria; NUC, nucleus.