The 5-Lipoxygenase pathway results in the formation of leukotrienes, including leukotriene B4 (LTB4), 5-oxo-6E,8Z,11Z,14Z-eicosatetranoic acid and the cysteinyl leukotrienes (LTC4, LTD4 and LTE4) and activates all four leukotriene receptors, BLT1, BLT2, cysLT1 and cysLT2. Zileuton is the only commercially available inhibitor of the 5-Lipoxygenase pathway. In a number of clinical trials, zileuton has been shown to improve airway function and inflammation, asthma symptom control and quality of life in asthmatics. Given the important role that leukotrienes play in airway inflammation, zileuton provides an additional therapeutic option in the management of chronic, persistent asthma, particularly those asthmatics with more severe disease. In addition, zileuton has shown promise in a number of other conditions, including upper airway inflammatory conditions, dermatological disease and chronic obstructive pulmonary disease. The development of new formulations, including a controlled release tablet formulation for b.i.d. dosing and an intravenous preparation for acute asthma exacerbations may enhance clinical utility and expand therapeutic indications.