In this review, we discuss recent advances made on histone methylation and its diverse functions in regulating gene expression. Methylation of histone polypeptides might be static and might mark a gene to be or not be transcribed. However, the decision to methylate or not methylate a specific residue in the histone polypeptides is an active process that requires coordination among different covalent modifications occurring at the amino termini of the histone polypeptides, the histone tails. Below, we summarize recent advances on histone methyltransferases, and we discuss histone methylation within the context of other histone tail modifications.