Non-typeable Haemophilus influenzae is a common cause of human disease and initiates infection by colonizing the upper respiratory tract. Based on information from histopathologic specimens and in vitro studies with human cells and tissues in culture, non-typeable H. influenzae is capable of efficient adherence and appreciable invasion, properties that facilitate the process of colonization. A number of adhesive factors exist, each recognizing a distinct host cell structure and influencing cellular binding specificity. In addition, at least three invasion pathways exist, including one resembling macropinocytosis, a second mediated via the PAF receptor and a third involving beta-glucan receptors. Organisms are also capable of disrupting cell-cell junctions and passing between cells to the subepithelial space.