Histamine released from mast cells and basophils is an important mediator of airway inflammation in asthma, particularly in the development of the early allergic response. Although histamine has been shown to contribute significantly to the bronchoconstrictor response to allergen or exercise, leukotrienes are likely to play a more prominent role in these responses in asthma. The improved specificity, tolerability, and safety profile of the second-generation H1-antagonists associated with anti-inflammatory activities and bronchodilator activities, may contribute to relieve the symptoms of the upper and lower airways in patients with coexistent mild seasonal asthma and allergic rhinitis. Considering the global rise in the prevalence of allergy and asthma, the suggestion that H1-antagonists may delay the onset of asthma in infants is of considerable interest and merits further assessment. Although it is unlikely that monotherapy with most currently available H1-antagonists will provide significant clinical benefit in asthma, the potential of combined antihistamine and antileukotriene therapy may prove useful, particularly in subjects with poor compliance to inhaled corticosteroid therapy.