From a functional standpoint, glycosyltransferases (GTases) comprise one the most diverse group of enzymes in existence. Every category of biopolymer (oligosaccharides, proteins, nucleic acids, and lipids) plus numerous natural products are modified by GTases, with remarkably varied effects. Given the structural and functional diversity of the products of glycosyl transfer combined with the often distant evolutionary relationships between glycosyltransferases, it is not surprising that sequence homologies between glycosyltransferases are low. What is surprising is that the majority of glycosyltransferases belong to only two structural superfamilies, implying that nature has come up with only a few solutions to the ubiquitous problem of how to catalyze glycosyl transfer. The conservation of GTase structure suggests that it will be simpler to manipulate glycosyltransferases for various applications than previously envisioned. A new age in glycoconjugate chemistry is beginning.