The classification of carbohydrate-active enzymes, presents a number of challenges to conciliate sequence and genome information with protein structure and reaction mechanisms. The principles of the sequence- and structure-based classification according to CAZy, combining structural and mechanistic information with bioinformatics, are described. In this chapter, we give a particular emphasis to the classification and description of glycosyltransferases relying on phospho-activated sugars. Issued from a limited number of protein folds, the corresponding diverse set of enzyme families was subdivided according to the nature of the phospho-activated sugar (mono- vs. diphospho-activated sugars; axial- vs. equatorial-linked glycosidic moieties; nature of activator) and the type of catalytic mechanism (inverting vs. retaining) to show that these features are usually strictly conserved at family level. Given the practical difficulties to determine glycosyltransferase activity, existing knowledge of the common features found at family level should be used to limit the range of activities to assess experimentally.