Besides DNA, RNA, proteins, and lipids, the other major macromolecular components of living systems are carbohydrates (hereafter generically called glycans). All mammalian cells and extracellular matrices contain a high density of glycan biomolecules, including glycoproteins, glycolipids, proteoglycans, and polysaccharides (3). Such glycans are among the most abundant organic molecules in nature, are essential for all living organisms, and participate in most biological processes (4), but they are also the most challenging to study. Unlike DNA and RNA or proteins, which are genetically coded and produced by template-drive processes, there is no uniform “glycocode,” and glycan biosynthesis relies on coordinated efforts of different enzymes and subcellular compartments in a cell-, tissue-, and species-specific manner. Furthermore, glycans are the most diverse biomolecules, constructed with building blocks selected from a large collection of structurally different monosaccharides, connected with a variety of glycosyl linkages, with the possibility of multiple branches and disparity of molecular weights. Lack of proper tools and user-friendly synthetic strategies, as well as their dynamic structural changes in response to environmental variations, add to the difficulties in analyzing, studying, and elucidating the structures and functions of complex glycans, especially those in living organisms. Therefore, glycans are ideal targets for applying the user-friendly click chemistry and bioorthogonal reactions.