Airway inflammation is a characteristic feature of allergic asthma. Central to the initiation and progression of the inflammatory process are allergen-specific T lymphocytes that attract eosinophils, mast cells, and B cells to the airways by the secretion of specific cytokines. The direction of T cell responses is influenced by co-stimulatory signals that modulate the antigen-specific signal delivered by the T cell receptor. In addition to the prototypic co-stimulatory molecule, CD28, a number of newly identified co-stimulatory molecules and their ligands have now been characterized. Over the past 5 years, the role of these molecules in the pathophysiology of allergen-mediated sensitization and airway inflammation has been extensively studied in animal models of allergic asthma. The aim of this review is to provide a detailed overview on recent studies in mice and preliminary findings in man and to discuss the potential therapeutic and preventive treatment strategies offered by interactions with co-stimulatory molecules for patients with allergic airway diseases.