The -methylation of specialized metabolites in plants is a unique decoration that provides structural and functional diversity of the metabolites with changes in chemical properties and intracellular localizations. The -methylation of flavonoids, which is a class of plant specialized metabolites, promotes their antimicrobial activities and liposolubility. Flavonoid -methyltransferases (FOMTs), which are responsible for the -methylation process of the flavonoid aglycone, generally accept a broad range of substrates across flavones, flavonols and lignin precursors, with different substrate preferences. Therefore, the characterization of FOMTs with the physiology roles of methoxylated flavonoids is useful for crop improvement and metabolic engineering. In this review, we summarized the chemodiversity and physiology roles of methoxylated flavonoids, which were already reported, and we performed a cross-species comparison to illustrate an overview of diversification and conserved catalytic sites of the flavonoid -methyltransferases.