Flagella contribute to the virulence of pathogenic bacteria through chemotaxis, adhesion to and invasion of host surfaces. Flagellin is the structural protein that forms the major portion of flagellar filaments. Thus, flagellin consists of a conserved domain that is widespread in bacterial species and is dedicated to filament polymerization. Conversely, mammalian hosts detect the conserved domain on flagellin monomers through Toll-like receptor (TLR) 5, which triggers proinflammatory and adaptive immune responses. This review describes the relationships among flagellin molecular structure, bacterial virulence and host defenses, with special emphasis on mucosal tissues.