Structural and functional features of mammalian S-adenosyl-methionine-dependent small molecule methyltransferases are reviewed. The methyltransferases have similar protomer molecular weights in the range of 25,000-35,000. Two common sequence motifs are found in all enzymes of known sequence. Whereas the kinetic mechanisms may be different, the methyltransferases in the free form bind S-adenosylmethionine. Most, if not all, of mammalian small molecule methyltransferases appear to have vicinal thiols in a catalytically important area of the enzyme.