Cancer is considered as one of the serious public health problems, and globally it was reported to be the second largest cause of death. The development of novel therapeutic anticancer agents is still in serious need. In this regard quinoline conjugated heterocyclic derivatives remain one of the most attractive class of compounds for anticancer development. Numerous recent reports evidenced that quinoline-heterocyclic hybrids displayed antiproliferative effect against different kinds of cancer cells via different mechanisms including the inhibition of a wide range of protein kinases such as PDK1, CDK2, topoisomerase, APE-1F, GFR3, HDM2, PI3K and others. The present review highlighted the anticancer potential of quinoline conjugated with different heterocycles such as azetidinone, benzimidazole, benzofuran, benzothiazole, coumarin, imidazole, indole, morpholine, oxadiazole, piperazine, pyrazole, pyrimidine, tetrazole, thiazole, triazole and others fused to or substituted directly to the quinoline nucleus or via intermediate chain or linker the in the twenty first century which could serve as a platform for pharmaceutical chemists to design and develop better anticancer candidates.