Galactosyltransferases are among the most represented enzymes in the glycosyltransferases superfamily. Galactosyltransferases bind UDP-α-D-galactose as the donor substrate and transfer the galactose to acceptor substrates that are as different as glycoproteins, glycosaminoglycans, glycolipids and, to some extent, small lipophilic molecules such as plant hormones. For the past decade, mammalian galactosyltransferases have been the center of interest for glycobiologists focused primarily on the discovery of their genes and on the characterization of their enzyme activity. In 1999, the first picture of the crystallographic structure of bovine β4GalT1 catalytic domain was revealed at 2.4Å resolution. This study was the beginning of a new structural approach to glycosyltransferases that focused on the description of their three-dimensional structure at atomic resolution with the objective of interpreting former enzymatic properties and understanding their reaction mechanism. This minireview is an attempt to describe the current status of the galactosyltransferase structure-function relationship in the context of the glycosyltransferase superfamily. The crystallographic structures of two bovine galactosyltransferases catalytic domains, those of β4GalT1 and α3GalT, will be discussed as well as their reaction mechanism.