In this chapter we outline the evolution of our understanding of the biological functions, genetics and regulation of enzymes of the GT2 and GT48 families of glycosyl transferases. The GT2 family is very large and includes enzymes encoded by the cellulose synthase gene superfamily, together with many other transferases with diverse substrate specificities that are distributed from the Archaea to humans. On the other hand, there are relatively few known members of the GT48 family, in which activities are limited to putative (1,3)-β-d-glucan synthases of embryophytes, fungi and yeasts. The review is focused on a number of individual case studies, which have been chosen on the basis of their biological and economical importance in plant biology. The history of our knowledge of (1,4)-β-d-glucan (cellulose) synthases and (1,3;1,4)-β-d-glucan synthases in plants will be reviewed as representatives of the GT2 family, while the (1,3)-β-d-glucan (or callose) synthases will be compared with these, as representatives of the GT48 family. These synthases have been extensively studied using biochemical techniques, but they are associated with membranes and are not easily purified. Emerging functional genomics technologies have been used to identify the genes encoding the cellulose synthases of the GT2 family, while new proteomics procedures have provided amino acid sequence that has in turn been applied to the identification of the GT48 (1,3)-β-d-glucan synthases of plants. The enzymes are involved in the synthesis of structurally similar polysaccharides, but appear to have evolved independently.