Non-histone methylations on lysine or arginine residues have been proved to be a common fashion of post-translational modification on proteins. The diversity of methylation on different proteins or different modifying modes, such as adding one, two, or three methyl groups, dynamically affects extensive biological outcomes, including gene expression, protein activities, protein stabilities, DNA replication, genome stability, RNA processing and so on. In the manuscript, we summarized the features of protein methylation and recent progress in non-histone methylation modifiers, identified methylation sites, as well as their corresponding biological functions. Particularly, crosstalk between methylation and other types of post-translational modifications and advances in defining non-histone methylation approaches will be highlighted.