To review the pharmacology, pharmacokinetics, clinical efficacy, and adverse effects of montelukast, a leukotriene receptor antagonist used to treat asthma, and to discuss the therapeutic role of montelukast as long-term medication and difficulties associated with the management of asthma. A MEDLINE search (up to May 1999) was conducted to identify relevant English-language publications, including preclinical studies, clinical trials, and recent reviews. All available published reports of controlled, clinical trials of montelukast in adults and children with asthma were summarized, including pharmacokinetic and pharmacologic effects of montelukast. Information on the safety and efficacy of montelukast was evaluated on the basis of patient selection, study design, methodology, and statistical significance as compared with placebo or inhaled corticosteroid treatment. Montelukast is approved for the prophylaxis and chronic treatment of asthma at a dose of 10 mg once daily for adolescents (> or =15 y) and adults and 5 mg once daily for children (6-14 y). In placebo-controlled clinical trials, montelukast significantly improved pulmonary lung function (as measured by forced expiratory volume in 1 sec), significantly reduced beta2-agonist use, and significantly improved patient-reported end points in adults and children (> or =6 y) with chronic asthma. In adults, a similar magnitude of improvement in lung function is seen with or without inhaled corticosteroid use; the effects of montelukast may be additive to those of inhaled corticosteroids and permit the reduction of the required dose of inhaled corticosteroids. In cases of exercise-induced asthma (adults and children), montelukast treatment attenuates the fall in pulmonary function following exercise. It attenuates both the early- and late-phase responses of asthma after allergen inhalation. Improvements in asthma control are similar in asthmatic patients who are aspirin-sensitive or not aspirin-sensitive and can be seen within one day of treatment. Tolerance does not develop, and the adverse events do not differ from those of placebo. Montelukast is indicated for the prophylaxis of chronic asthma in adults and children (> or =6 y). It may be considered for use as first-line therapy in patients with mild persistent asthma or for additional control in patients who are still symptomatic while receiving treatment with inhaled corticosteroids. It may also be used for additional control in aspirin-sensitive asthmatic patients. Consideration may be given for using montelukast to allow tapering of the dose of inhaled corticosteroids while maintaining clinical stability. Chronic treatment with montelukast can provide additional control of symptoms during exercise, but inhaled beta2-agonists remain first-line therapy for prophylaxis and treatment.