An endogenous defect in beta(2)-adrenoceptors that results in impaired relaxation of airway smooth muscle was originally proposed as a putative underlying cause of the asthmatic condition. Short-acting beta(2)-adrenoceptor agonists such as salbutamol are still recommended for relieving acute episodes of bronchial smooth muscle spasm. Twice-daily long-acting beta(2)-adrenoceptor agonists (LABAs) such as salmeterol are advocated for use as add-on bronchodilator therapies to inhaled corticosteroids such as beclomethasone, which are used as first-line anti-inflammatory therapy. There is recent evidence of increased asthma exacerbations and associated deaths in subjects taking salmeterol compared with those taking placebo. My opinion is that, in certain situations, the use of LABAs could have adverse effects on asthma control because of the particular pharmacological properties of this class of drug. In this article, I examine the possible pharmacological mechanisms and use of LABAs in certain situations, which are relevant to the benefits and risks of these drugs in asthma.