Histone methylation, which mainly occurs at lysine and arginine residues located on the N-terminal tails of the core histones, is one of the most studied post-translational modification marks. Protein lysine methyltransferases (PKMTs) and protein arginine methyltransferases (PRMTs) are two of the writers responsible for adding the methyl marks to histones. Recently, it has also been shown that these writers are capable of methylating other functionally important proteins, including p53, ERα, pRb, TAF10, and HIV tat. Growing evidence suggests that protein lysine methyltransferases (PKMTs) and protein arginine methyltransferases (PRMTs) are associated with the development of various human diseases, including cancer, inflammation, and psychiatric disorders.