Lipooligosaccharides (LOSs) are the major glycolipids expressed on mucosal Gram-negative bacteria, including members of the genera Neisseria, Haemophilus, Bordetella, and Branhamella. They can also be expressed on some enteric bacteria such as Campylobacter jejuni and Campylobacter coli strains. LOS is analogous to the lipopolysaccharide (LPS) found in other Gram-negative families. LOSs share similar lipid A structures with an identical array of functional activities as LPSs. LOSs lack O-antigen units with the LOS oligosaccharide structures limited to 10 saccharide units. The LOS species of pathogenic Neisseria can play a major role in pathogenesis through enhancing the resistance of the organism to killing by normal human serum. Other distinguishing characteristics of LOS are the structural and antigenic similarity of some LOS species to human glycolipids and the potential for certain LOSs to be modified in vivo by host substances or secretions. These modifications of LOS in different environments of the host result in synthesis of new LOS structures that probably benefit the survival of the pathogen. The LOS of N. gonorrhoeae can act as a ligand of human receptors, promoting invasion of host cells. It is becoming clearer that LOSs are crucial factors in the pathogenesis of bacteria that express them.