The recent development of metabolic oligosaccharide engineering combined with bioorthogonal reactions is providing unique opportunities to detect, image, and isolate glycoconjugates of living cells, tissues, and model organisms. In this methodology, exogenously-supplied non-natural sugars are fed to cells and employed by the biosynthetic machinery for the biosynthesis of neoglycoconjugates. In this way, reactive functional groups such as ketones, azides, and thiols have been incorporated into sialic acid, galactosamine, glucosamine, and fucose moieties of glycoconjugates. A range of bioorthogonal reactions have been described that functionalize the chemical 'tags' for imaging, isolation, and drug delivery.