Antibiotics are undeniably a gift to humanity, since they have prevented the loss of millions of lives due to the elimination of infectious bacteria. This review was based on the antimicrobial activity of Isatin-hybrids through extensive literature survey. Isatin, also called 1H-indol-2,3-dione, is a naturally occurring heterocyclic chemical found in several plants across the globe. The amino acid proline reacts with isatin, another component of coal tar, to produce a blue derivative. It is widely dispersed in the human CNS, peripheral tissues, and bodily fluids, and is known to be a metabolite of tryptophan or epinephrine. Recently, it has been discovered that 5,7- dibromo-N-(p-trifluoromethylbenzyl)- isatin exhibits a selective inhibitory effect against lymphoma and leukemic cancer cell lines compared to freshly separated, nontransformed human peripheral blood lymphocytes. Many researchers have shown that isatin-hybrids are active against various microbes, protozoans, parasites etc. These analogues also demonstrated significant anti-plasmodial action. Thus, it can be concluded that isatin-hybrids have numerous pharmacological potentials in terms of antimicrobial, anticancer, anthelmintic, antimalarial, anti-plasmodial etc. and such moieties are of great interest for promising researches.