Decreased responsiveness to beta-adrenergic receptor agonists is a characteristic feature of human asthma. This review summarizes data regarding the impact of chronic beta agonist stimulation, cytokines, prostanoids and other factors on beta-adrenergic responses in human airway smooth muscle, as well as the impact of polymorphisms of the beta(2)-adrenergic receptor on these responses. Effects of beta-agonists on both airway smooth muscle relaxation and gene expression are considered. Understanding the regulation of beta-adrenergic responses in airway smooth muscle cells may prove to be an important step in improving the efficacy of beta-agonists for the treatment of asthma.