Cells are treated with unnatural, tagged derivatives of naturally occurring monosaccharides, such as the peracetylated azide-tagged derivatives of ManNAc and GlcNAc shown (top left). After uptake and deprotection of the acetyl groups (bottom left), the metabolic precursors enter the cellular pathways for conversion into the corresponding CMP- or UDP-activated donors, which are then used for glycan biosynthesis. ManNAc derivatives are incorporated as sialic acids into cell surface glycans (A) while GlcNAc derivatives label intracellular proteins that are targets for O-GlcNAc modification (B). The azide-tagged glycans can be labelled by bioorthogonal ligation reactions such as the strain-promoted (A) or the copper(I)-catalysed (B) azide-alkyne cycloaddition.