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With the identification of disease source and symptoms, many chemical entities were developed naturally and synthetically for administration as a potential antimalarial drug. The major classes of approved antimalarial drugs that are governed as first\u2010line treatment in tropical and subtropical areas include quinolines, naphthoquinones, antifolates, 8\u2010aminoquinolines, and endoperoxides. However, the efficacy of antimalarial drugs has decreased due to ongoing multidrug resistance problem to current drugs. With increasing resistance to the current antimalarial artemisinin and its combination therapies, malaria prophylaxis has declined gradually. New\u2010generation antimalarial and novel drug target are required to check the incidence of malaria resistance. This review summarizes the emergence of multidrug resistance to known antimalarial and the development of new antimalarial to resolve drug resistance condition. 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