Various organic chelating agents have many applications in treating the several diseases and they act as antibacterial, antiviral, antimalarial and cytotoxic agents. Among the organic chelating agents thiosemicarbazones and their derivatives play a unique role in various fields of medicine. Thiosemicarbazones and their derivatives find a numerous applications and among them cytotoxic activity occupies a major portion due to the severity of the cancer treatment. In this present chapter we described and discussed the cytotoxic activity of thiosemicarbazones, their derivatives and various metal complexes of them. For this purpose, we reviewed the research articles published in various reputed international journals since 35 years. We summarized the results of those research findings and it is found that among the various metal ions, mostly the platinum and palladium complexes are effective cytotoxic agents than other metal complexes.