Lipopolysaccharide 3-Deoxy-D-manno-octulosonic Acid (KDO) is an essential component of the lipopolysaccharide (LPS) layer. Cells defective in KDO biosynthesis have a compromised LPS and are usually less pathogenic and more susceptible to antibiotics. The enzyme 3-deoxy-manno-octulosonate cytidylyltransferase (CMP-KDO synthetase; CKS) catalyzes the activation of 3-deoxy-D-manno-octulosonate (or 2-keto-3-deoxy-manno-octonic acid; KDO) by forming CMP-KDO. The enzymes belong to cytidylyltransferase protein family being a part of GT-A clan that contains diverse glycosyltransferases that possess a Rossmann like fold. KDO is an essential component of lipopolysaccharides (LPS) in Gram-negative bacteria. Incorporation of KDO into LPS requires its activation by 3-deoxy-manno-octulosonate CKS. CKS is an attractive target for the development of antibacterial agents.