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The resistance of malaria parasites to widely used drugs prompted an upsurge in the development of new drugs with novel mechanism of action, and re- evaluation of the existing drugs to overcome the resistance problem. A number of new potential target pathways have already been identified and efforts to develop lead compounds for these putative targets hopefully will allow treatment of malaria infections in a uniform sustained way. Considerable research efforts were directed in the areas of chloroquine drug resistance reversal agents. Careful development of some bisquinolines, which are free of toxic side effect, 4-anilinoquinolines and modified chloroquine analogs may be helpful to obtain drug candidates that inhibit the growth of chloroquine sensitive and resistant parasites. In the past several years, new structural classes of antimalarial agents, target based antimalarial agents, iron chelators have made some interesting and promising lead molecules available for further optimization to provide compounds for clinical development.