For treatment of moderate and severe persistent asthma the National Heart Lung Blood Institute (NHLBI) Guidelines offer the alternative of moderately high doses of inhaled corticosteroids alone or a lower dose of inhaled corticosteroids combined with a long-acting bronchodilator. Three classes of drugs qualify for the combination with inhaled corticosteroids. They are long-acting beta-agonists, leukotriene receptor antagonists, and sustained-release theophylline. Each class of drug has been shown, when combined with inhaled corticosteroids, to provide equal or better asthma control than a higher dose of inhaled corticosteroids alone. Direct comparisons indicate that, of the three classes, the long-acting beta-agonists are the most effective. Furthermore, initial concerns regarding their masking airway inflammation appear to be unfounded, because when combined with inhaled corticosteroids, the long-acting beta-agonists further decrease both the frequency and the severity of asthma exacerbations and appear to have some modulating effect on airway inflammation.