Evidence from clinical trials and experience derived from managing patients with asthma justify a broader role for leukotriene (LT) blockers in asthma management than that recommended by the National Asthma Education and Prevention Program and the NIH Heart, Lung and Blood Institute treatment guidelines. Many published clinical trials, reviews, and case reports have suggested important new applications of LT blockers (ie, montelukast, zafirlukast, pranlukast, and zileuton) in several diseases in which leukotrienes play a pathogenic role. These include paranasal sinus disease, allergic fungal sinusitis, migraine, chronic urticaria, atopic dermatitis, chronic obstructive pulmonary disease, allergic conjunctivitis, mastocytosis, bronchiolitis, idiopathic pulmonary fibrosis, interstitial cystitis, and irritable bowel syndrome. Although double-blind, randomized, placebo-controlled trials are needed to confirm the effects that these drugs may have in these diseases, the aim of this short review is to delineate the future roles that these drugs may have in the management of these conditions.