X-ray crystallography and kinetic isotopic effects applied to glycosyl-processing enzymes in complex with their substrates or inhibitors allowed deciphering of the sugar ring conformation at the atomic level. This information, crucial for the development of potent and selective inhibitors of these enzymes, has been extensively exploited to design conformationally restricted sugar analogues. This chapter gives an overview of the main classes of conformationally restricted sugar analogues aimed at interfering with hydrolytic and non-hydrolytic glycosyl-processing enzymes that have been reported in the literature.