Multicomponent reactions (MCRs) have emerged as a powerful strategy in synthetic organic chemistry due to their widespread applications in drug discovery and development. MCRs are flexible transformations in which three or more substrates react to form structurally complex products with high atomic efficiency. They are being increasingly appreciated as a highly exploratory and evolutionary tool by the medicinal chemistry community, opening the door to more sustainable, cost-effective and rapid synthesis of biologically active molecules. In recent years, MCR-based synthetic strategies have found extensive application in the field of drug discovery, and several anticancer drugs have been synthesized through MCRs. In this review, we present an overview of representative and recent literature examples documenting different approaches and applications of MCRs in the development of new anticancer drugs.