In persons with asthma, the cysteinyl leukotrienes possess multiple inflammatory properties in vitro and have long been considered to be a potentially important mediator of asthma and an attractive target for therapeutic intervention. Controlled clinical trials have documented the efficacy of leukotriene receptor antagonists in asthma treatment, but reservations about their use for asthma therapy center on two main issues: the heterogeneity of patient responses and their reduced potency relative to other asthma medications. For example, leukotriene receptor antagonists also have been shown to be less efficacious than inhaled corticosteroids for several end points, including symptom relief, reduced markers of inflammation, and improved pulmonary function. This review explores several underappreciated aspects of asthma therapy: heterogeneity of patient responses to medication, the failure of symptoms to correlate with commonly used end points, and the potential of delivery to distal airways for producing important and novel benefits. (J Allergy Clin Immunol 2003;111:S62-70.)