Fluorinated compounds play a unique role in the development of novel lead compounds in both medicinal chemistry and modern crop protection. The introduction of fluorine atom always produces significant changes in the physical properties and often improves the biological activity of target moleculars. Multicomponent reactions (MCRs) are becoming a vastly more powerful tool for the creation of molecule libraries due to their highly convergent diversity, efficiency, selectivity, and atom economy. This paper reviewed growing applications of the trifluoromethyl, difluoromethyl, and fluoroalkyl building blocks as one of components in the multicomponent reactions for the construction of complex and diverse fluorinated molecules, respectively.