The human β₂-adrenoceptor is a member of the 7-transmembrane family of receptors, encoded by a gene on chromosome 5, and widely distributed in the respiratory tract. Intracellular signaling after β₂-adrenoceptor activation is largely affected through cyclic adenosine monophosphate and protein kinase A. Differences in the mechanism of interaction of short- and long-acting β₂-agonists and the β₂-receptor are reflected in the kinetics of airway smooth muscle relaxation and the onset and duration of bronchodilation in asthmatic patients. β-Adrenoceptor desensitization associated with prolonged β₂-agonist activation differs depending on the cell type and is reflected in different profiles of clinical tolerance to chronic β₂-agonist therapy. A number of genetic polymorphisms of the β₂-receptor have been described that appear to alter the behavior of the receptor, including the response to β₂-agonists. The synergy between the β₂-receptor and the glucocorticoid receptor functions has implications for the combined use of β₂-agonists and corticosteroids in the treatment of respiratory disease.