Antihistamines have long been utilized in the symptomatic management (antihistaminic effects) of allergic rhinitis and conjunctivitis. Investigation into the nonsedating second-generation antihistamines suggests that they also possess antiinflammatory activity, and may be useful in the management of inflammation associated with allergic airway disease. In vitro studies have shown that these antihistamines decrease the migration and activation of eosinophils and diminish the release of pro-inflammatory mediators from mast cells and basophils after induction by immunological and nonimmunological stimuli. In vivo studies have also demonstrated that these antihistamines decrease inflammatory cell infiltration in allergic airway disease, and mediator release from mast cells and basophils. Epithelial cells, due to their spatial arrangement and predominance in the airways, play a pivotal role in the etiology of airway disease. There is evidence that antihistamines may modulate airway inflammation by influencing the activity of these airway epithelial cells. Studies have shown that expression of adhesion molecules on epithelial cells is decreased by second-generation antihistamines. Collectively, these studies suggest that second-generation H1-histamine receptor antagonists have potential use either as safe antiinflammatory alternatives to corticosteroids or as rescue medication in combination with corticosteroids for the management of severe airway disease.