While this progress in elucidating molecular details of quinoline pharmacology is critical, importantly, a recent report suggests that drug-heme interactions are likely not the only way in which the drug exerts a toxic effect -it is only one layer of a more complex collection of effects [28] . In this paper, cytotoxicity of CQ against different stages of iRBC parasites was quantified for both CQS and CQR parasites. Surprisingly, CQ was found to be nearly as toxic to rings and schizonts as to trophozoites. Although recent work by Elliot and colleagues shows that ring parasites do indeed begin degrading some small amounts of Hb, as proposed earlier, schizonts do not metabolize Hb nor produce Hz as trophozoites do [29, 30] . The simple conclusion then is that different forms of free FPIX are not likely to be the only targets of quinoline drugs. Even more surprisingly, this study also demonstrated that P. falciparum CQ-resistance transporter (PfCRT) mutations confer approximately similar levels of CQ resistance to all three iRBC stages [28] . Since a fully formed DV membrane does not exist for ring stage parasites, this suggests that the PfCRT protein (see later section on PfCRT) is likely to have additional locations within the parasite, and more than one physiological function. The next few years of research will yield a more complex, but more complete molecular picture of quinoline antimalarial pharmacology. Although some new pharmacophores are in development, the three major classes of antimalarial drugs are the quinolines (e.g., CQ, mefloquine [MQ] and QN), the antifolates (pyrimethamine and cycloguanil), which both poison nucleotide biosynthesis by limiting essential folate cofactors, and the reactive endoperoxides (artemisin and derivatives) whose action is not well understood. Resistance to the first two classes is profound and widespread, and resistance to the third may be beginning to appear [31] . CQR parasites were first noticed 10-20 years after the introduction of the compound and CQ resistance was well documented in 1959 in Asia. Attempts to eliminate malaria (via insecticides and prophylactic use of CQ) possibly further promoted CQ resistance.