How safe is the use of long-acting beta2-adrenergic agonists in the treatment of asthma? Recently, several warnings have been issued by the US Food and Drug Administration and the World Health Organization concerning the safety of long-acting beta2-adrenergic agonists in the treatment of patients with asthma. These warnings were based on data from the 'Salmeterol multicenter asthma research trial' (SMART) published in January 2006. This randomized, placebo-controlled trial studied the effects of the addition of either salmeterol or placebo to the usual medication regime, with respiratory-related deaths and life-threatening events as primary endpoints. There were no significant differences between treatments for these conditions. There were small, but statistically significant increases in respiratory-related and asthma-related deaths, and combined asthma-related deaths, as well as life-threatening events in the total population receiving salmeterol. It is not clear whether the concomitant use of inhaled corticosteroids prevents an increased risk of such events. If asthma is not well-controlled by moderate doses of inhaled steroids, the respiratory and non-respiratory factors that elicit asthma attacks should be reduced and special attention paid to therapy compliance and the correct use ofinhalers. Treatment options including intensifying anti-inflammatory treatment by the use of inhaled corticosteroids which give increased peripheral lung deposition or the addition ofleukotriene receptor antagonists should also be considered before prescribing long-acting beta2-adrenergic agonists.