In mammals, DNA methylation, characterized by the transfer of the methyl group from S-adenosylmethionines to a base (mainly referred to cytosine), acts as a major epigenetic modification. In parallel to DNA sequences arrangement, modification of methylation to DNA sequences has far-reaching influence on biological functions and activities, for it involves controlling gene transcription, regulating chromatin structure, sustaining genome stability and integrity, maintaining parental imprinting and X-chromosome inactivation, suppressing homologous recombination as well as limiting transposable elements, during which DNA methyltransferases (DNMTs) and methyl-binding proteins play important roles. Their aberrance can give rise to dysregulation of gene expression, cell maltransformation and so on. Hence, it is necessary to gain a good understanding of these two important kinds of proteins, which will help to better investigate the epigenetic mechanisms and manipulate the modifications according to our will based on its reversibility. Here we briefly review our current understanding of DNMTs and methyl-binding proteins in mammals.