Inhaled beta(2)-adrenoceptor agonists are by far the most effective and safe bronchodilators currently available. They have not been surpassed by any other bronchodilating principle. The way to this position has been long and started with the first successful treatment of acute, severe asthma with s.c. injections of adrenaline 100 years ago. Over the years, synthetic congeners of adrenaline have been produced and tested for their pharmacological properties. During the first decades, little attention was given airway smooth muscle. The discovery of isoprenaline in 1940 was the first major step towards selective bronchodilation. This compound became a key tool for the classification of adrenoceptors into alpha and beta. Salbutamol and terbutaline were the first to show a significant attenuation of the cardiostimulant effect and confirmed the subdivision of beta-adrenoceptors into beta(1) and beta(2). Much effort was made to eliminate the next dose-limiting side effect, skeletal muscle tremor but in vain. Prolonged duration of action was achieved in three ways: with bambuterol, an orally active carbamate ester prodrug of terbutaline, salmeterol, an inhaled beta(2)-adrenoceptor agonist emerging from a purposeful research project, and formoterol which was found, accidentally, to have a long duration of action when inhaled. Throughout the 20th century, beta-adrenoceptor agonists have been developed and marketed as racemates. The pharmacological activity usually resides in the (R)-enantiomer. Despite claims for the opposite, there is so far no compelling evidence that the presence of the less active (S)-enantiomer is of any harm to the patient. One hundred years of experience of structural modifications of adrenaline has shown that the possibilities to modify the properties of this endogenous prototype appear to be unlimited.