In view of the large body of evidence for the role of histamine and cysteinyl leukotrienes (CysLT1) in the pathogenesis of allergic rhinitis (AR) and asthma, there has been a surge in the development of histamine H1 and CysLT1 receptor antagonists (H1 antihistamines and leukotriene antagonists, respectively) for the treatment of these conditions. Current treatment guidelines recommend the use of oral H1 antihistamines as first-choice treatment for intermittent or persistent AR and the leukotriene antagonists, either as alternative or add-on therapy to inhaled corticosteroids, for mild-to-moderate persistent asthma. However, recent studies, using a variety of traditional and novel outcome measures, have suggested that the H1 antihistamines and leukotriene receptor antagonists (LTRAs) may be effective in both asthma and AR. However, these studies have provided conflicting evidence as to whether H1 antihistamines and the leukotriene antagonists have the potential for additivity of response, when used as combination therapy in AR. There are also preliminary data showing that H1 antihistamines, like LTRAs, may further reduce inflammation, when used as add-on therapy to inhaled corticosteroids in patients with mild-to-moderate persistent asthma. The clinical relevance of these findings, however, is presently not clear and also, the observed effects of these agents are likely to be dependent on the type of outcome measures used in these studies. Further studies are therefore clearly required to evaluate the effects of combined histamine H1 and CysLT1 receptor antagonists in patients with more severe disease over the longer term, particularly to evaluate asthma exacerbations and airway remodelling. Furthermore, it will be important to assess the potential for treating the unified airway in patients with concomitant asthma and AR in terms of comparing combined mediator antagonism with topical corticosteroid therapy.