In the normal respiratory tract, the airway epithelial surface is protected from pathogenic bacterial colonization by the mucociliary clearance. The mucins present in the gel mucus layer exhibit a high diversity of carbohydrate receptors that allow specific bacterial recognition followed by bacterial and mucus elimination. As soon as the mucociliary clearance mechanism is impaired, the bacterial attachment to mucins in association with mucus stasis represent critical pathways for bacterial colonization of the airway epithelium. Several sources of injury may damage the epithelial integrity and induce partial or complete epithelial shedding, exposing cellular receptors and unmasked extracellular matrix (ECM) components that can be recognized by bacterial adhesins. Laminin and type I and IV collagens represent sites of Pseudomonas aeruginosa attachment to the ECM components. During airway epithelium repair after injury, particularly in cystic fibrosis (CF), the repairing cells exhibit apical receptors such as asialylated gangliosides (asialo GM1) to which P. aeruginosa adheres. The identification of the different receptors for P. aeruginosa, present either on the ECM proteins or on the apical surface of the remodeled airway epithelium, particularly in repairing respiratory CF epithelial cells, is a prerequisite to further therapeutic strategies to prevent airway colonization by P. aeruginosa.