The sialic acids are acidic monosaccharides typically found at the outermost ends of the sugar chains of animal glycoconjugates. They potentially can inhibit intermolecular and intercellular interactions by virtue of their negative charge. However, they can also act as critical components of ligands recognized by a variety of proteins of animal, plant, and microbial origin (sialic acid binding lectins). Recognition can be affected by specific structural variations and modifications of sialic acids, their linkage to the underlying sugar chain, the structure of these chains, and the nature of the glycoconjugate to which they are attached. Presented here is a summary of the various proteins that can recognize and bind to this family of monosaccharides, comparing and contrasting the structural requirements and mechanisms involved in binding. Particular attention is focused on the recently evolving information about sialic acid recognition by certain C-type lectins (the selectins), I-type lectins (e.g., CD22 a...