Protein post-translational modifications, as an important step in protein maturation, participate in the regulation of diverse protein biological functions. Methylation is one of the modifications and plays multiple roles in cellular processes, ranging from eukaryotes to prokaryotes. Protein methylation occurs on various amino acid residues, such as lysine, arginine, glutamine and others. This review summarized the progress in protein methylation, including both eukaryote and prokaryote, as well as histone and non-histone proteins.