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Cyanoacetylindoles (CAIs) are easily obtained from the reaction of indoles and cyanoacetic acid, and are used as versatile starting materials in the synthesis of different heterocycles. This review focuses on the application of CAIs to generate a large diversity of indolyl heterocycles such as pyrazoles, triazoles, pyridines, dihydropyridines, pyrimidines, ozathiols, thiophenes, oxazoles, quinolines and many other complex heterocycles.