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We herein describe the first review which aims to focus soberly the various synthetic methods and chemical reactions of chloroquinoline-3-carbonitrile derivatives. The reactions are subdivided into groups that cover reactions of chloro substituent at 2 or 4 and 2,4 positions, as well as cyano substituent at 3 position and reactions which involve both groups. Most types of reactions have been successfully applied and used in the production of biologically active compounds.