This chapter explores the biochemistry and physiology of the target sites of melanin biosynthesis inhibitors (MBIs), an overview of their unique mode of action, and perspectives of related future research. Studies on the mode of action of MBIs shed light on the biochemical functions of appressoria and revealed the importance of melanin biosynthesis for pathogenicity. Melanin denotes a black pigment of biological origin, but generally melanins are envisioned as pigments consisting of polymeric phenolic compounds. Thus, certain brown, red, yellow, green, or blue pigments with similar chemical structures are occasionally referred to as melanins. Furthermore, the antipenetrant activity of MBIs was shown to be accompanied by the marked inhibition of appressorial melanization of Pyricularia oryzae. Most MBIs have been developed empirically on the basis of conventional screening systems. However, elucidation of fungal metabolisms that are essential for the expression of pathogenicity should provide promising and unique targets for the development of new disease-control agents.