The glycan chains of vertebrate glycoconjugates are composed mostly of five-and six-carbon sugars. One striking exception is the family of sialic acids (Sia), which are R-keto acids with a nine-carbon backbone. Several other features of sialic acids are unusual. First, they typically occupy the distal end of glycan chains. This “outermost” location makes them suitable for interaction with other cells and with environmental agents, and there are numerous examples of such interactions (described later in this review). Second, sialic acids are subject to a remarkable number of modifications, generating a diverse family of more than 50 structurally distinct molecules (Table 1). Third, unlike the other vertebrate monosaccharides, sialic acids are not ubiquitous in nature and seem to be predominantly found in two distinct branches of the tree of life: in the deuterostome lineage of animals (vertebrates and a few higher invertebrates such as starfish) and in certain types of bacteria. A fourth unusual feature of sialic acids is that they are synthesized via condensation of a neutral six-carbon unit with the three-carbon molecule pyruvate. Finally, sialic acids are unusual in the nature of their high-energy nucleotide sugar