The reversible hydrolytic property of glycosyl hydrolases (GHs) as well as their acceptance of aglycones other than water has provided the abilities of GHs in synthesizing glycosides. Together with desirable physiochemical properties of glycosides and their high commercial values, research interests have been aroused to investigate the synthetic other than the hydrolytic properties of GHs. On the other hand, just like the esterification processes catalyzed by lipases, GH synthetic effectiveness is strongly obstructed by water both thermodynamically and kinetically. Medium engineering by involving organic solvents can be a viable approach to alleviate the obstacles caused by water. However, as native hydrolyases function in water-enriched environments, most GHs display poor catalytic performance in the presence of organic solvents. Some GHs from thermophiles are more tolerant to organic solvents due to their robust folded structures with strong residue interactions. Other than native sources, immobilization, protein engineering, employment of surfactant, and lyophilization have been proved to enhance the GH stability from the native state, which opens up the possibilities for GHs to be employed in unconventional media as synthases.