Asthma is a chronic inflammatory disease affecting over 300 million people worldwide. The common association with allergic rhinitis and the presence of proinflammatory cells and mediators in the circulation of patients qualify asthma as a systemic disease. This characteristic and the fact that the gold-standard therapy for persistent asthma, inhaled corticosteroids, cannot suppress all components of airway inflammation and fail to adequately penetrate into the small airways, warrant the quest for effective systemic anti-asthma therapies. This review describes the most important controlled studies of montelukast, a once-daily leukotriene receptor antagonist, in asthma and allergic rhinitis in both adults and children. Montelukast is a systemically active drug with a targeted, dual mechanism of action, acting both as a bronchodilator and anti-inflammatory. In patients of all ages, montelukast has shown a favorable safety profile and was well-tolerated. Both as monotherapy or in combination with inhaled corticosteroids, montelukast produced clinically relevant improvements in asthma-related parameters, including symptoms, lung function parameters, quality of life and the number of asthma exacerbations. Furthermore, bronchoprotective effects have been reported both against specific and nonspecific bronchoactive stimuli. Similarly, in patients with allergic rhinitis, montelukast produced substantial improvements in symptoms and quality of life. Long-term studies aimed to determine its effects on airway remodeling are still lacking.