Despite concerns in the 1970s and 1980s about the safety of short-acting beta2-agonists, it is now generally accepted that these agents, used at appropriate doses, provide safe and effective treatment for asthma symptoms. After their introduction, beta2-agonists with a long duration of action--formoterol and salmeterol--became widely used as maintenance therapy with inhaled corticosteroids (ICS). Both beta2-agonists are well tolerated in long-term studies, with no reduction in lung function observed over time, indicating a lack of clinically relevant tolerance development in patients with asthma and COPD. High-dose studies have indicated that formoterol produces systemic effects of similar duration to, but less pronounced than, salbutamol and terbutaline. Formoterol produces long-lasting bronchoprotection against exercise-induced bronchoconstriction, even in patients receiving regular maintenance therapy; its fast onset of effect (similar to salbutamol) allows formoterol to be used as a reliever. Clinically the safety of formoterol and salmeterol has been demonstrated in several studies, both with ICS and alone.