Use of the potent bronchodilators, beta 2-adrenoceptor agonists, has been a cornerstone of the treatment of obstructive lung disease, especially asthma, for the past 30 years. However, the occurrence of side effects and the development of tolerance have been discussed as limitations to their use. beta 2-Adrenoceptors are located on the surface of most cell types throughout the human body, and treatment with beta 2-agonists may exert effects in a wide variety of tissues. As with other pharmacological receptors, beta 2-adrenoceptors in most tissues develop tolerance as a result of continuous beta 2-stimulation. However, the bronchodilatory effect appears to be unaffected by the development of tolerance. Interestingly, most studies have yielded evidence suggesting tolerance development regarding protection against bronchoconstrictor stimuli such as methacholine, adenosine and exercise. Although the protective effect of a beta 2-agonist becomes attenuated with continuous treatment, this tolerance is partial and adequate residual protective effect remains.