Antihistamines have mostly been used in the management of allergic rhinitis, primarily for their symptomatic relief. Recent studies, however, have suggested that the non-sedating second-generation antihistamines also possess anti-inflammatory activity, and consequently may be useful in the management of inflammation in allergic airways disease. Several in vivo studies have demonstrated that antihistamines decrease inflammatory cell infiltration in allergic disease, mediator release from mast/basophil cells, and the expression of adhesion molecules on epithelial cells. Similarly, in vitro studies have demonstrated that antihistamines decrease the migration and activation of eosinophils and the release of pro-inflammatory mediators from mast/basophil cells, induced by immunological and non-immunological stimuli. More recent evidence suggests that the antihistamines may modulate airway inflammation by influencing the activity of airway epithelial cells, which due to their spatial arrangement and predominance in the airways, are thought to play a pivotal role in the aetiology of airway disease. We and others have demonstrated that antihistamines attenuate allergen- or chemical-induced expression and/or release of mediators which influence the activity of inflammatory cells, such as eosinophils, mast cells, basophils and lymphocytes, known to be involved in the pathogenesis of allergic airway diseases. Collectively, these studies suggest that second-generation H1-histamine receptor antagonists may have potential use either as safe anti-inflammatory alternatives to corticosteroids, or as rescue medication in combination with corticosteroids, for the management of severe airway disease.