Pseudomonas aeruginosa lipopolysaccharide is a major virulence factor, initiator of inflammation and target for effective immunity. Pseudomonas aeruginosa is one of the most important bacterial pathogens encountered by immunocompromised hosts and patients with cystic fibrosis (CF), and the lipopolysaccharide (LPS) elaborated by this organism is a key factor in virulence as well as both innate and acquired host responses to infection. The molecule has a fair degree of heterogeneity in its lipid A and O-antigen structure, and elaborates two different outer-core glycoforms, of which only one is ligated to the O-antigen. A close relatedness between the chemical structures and genes encoding biosynthetic enzymes has been established, with 11 major O-antigen groups identified. The O-antigen is a major target for protective immunity as evidenced by numerous animal studies, but attempts, to date, to produce a human vaccine targeting these epitopes have not been successful.