In principle, genetics, physiology and biochemistry related to altered FPIX chemistry and membrane transport now defines CQ resistance. It is my suspicion that permutations of the above will ultimately be shown to define resistance to all other quinolines (QN, AQ, MQ and so on), to acridines, xanthones and reactive endoperoxides, but probably not to antifolates, for which resistance involves other distinct pathways [93] . That is, at least three genes (pfcrt, pfmdr1 and pfnhe) have been identified that, in various allelic combinations, confer what we now understand to be a spectrum of antimalarial multidrug resistance phenomena. The molecular function of at least two of these is becoming clearer via a combination of new chemical biology, artificial gene construction, and tried and trusted membrane biochemistry techniques. The physiologic and pharmacologic consequences of their function is at least qualitatively defined, and although there is still much more to do at the molecular level, the field has come a very long way in the 9 years since the identification of PfCRT. We can be hopeful that, based on this information, new quinolines effective against CQR malaria will prove increasingly easier to design and synthesize. In fact, the author suggests that this hope is even now being realized [91, 94, 95] . This work complements continued uses and combination therapies involving other quinoline derivatives such as pyronaridine (an aza-acridine) [96] , piperaquine [97] and isoquine [98] as well as other heme-binding pharmacophores such as the very exciting xanthones pioneered by Riscoe and colleagues [99] . History repeatedly teaches us that even with the emergence of CQ resistance, inexpensive quinolines and related compounds can still be effective.