2-Pyridones are now in great interest as promising drug candidates, because of its nucleobase-like structure and various directions of hydrogen bonds. Among numerous reports of its synthesis, direct installation of substituents into already-made 2-pyridone “platform” through C-H bond activation is arguably one of the most efficient methods to access to its derivatives. In this review, several elegant methods on the C-H functionalization of 2-pyridones are discussed.