Ninhydrin has been utilized in many heterocyclic preparations and considered as an important building block in organic synthesis. There is a wide range of reactions that include ninhydrin in the synthesis of heterocyclic compounds. This review highlights the advances in the use of ninhydrin as starting material in the synthesis of various organic compounds and drugs in a fully comprehensive way, from its first isolation in 1910 to the end of 2013. There is also a diversity of multi-component reactions of ninhydrin and we highlight the recent reports in this review.