Corticosteroids are often used in combination with beta2-agonist and anticholinergic bronchodilators in the treatment of chronic obstructive pulmonary disease (COPD). Corticosteroids activate the beta2-receptor gene, increasing receptor number and decreasing desensitization. Long-acting beta2-agonists prime the glucocorticoid receptor and enhance nuclear translocation via activation of CCAAT enhancer binding protein-alpha. Corticosteroids can also increase prejunctional auto-inhibitory M2-receptor gene expression in airway smooth muscle. There is evidence of a synergistic inhibition of cytokine and chemokine release from alveolar macrophages, epithelial cells, and mucosal glands and enhanced respiratory cytoprotection against viral and bacterial infection when a corticosteroid is combined with salmeterol. In airway smooth muscle, corticosteroids inhibit the contractile effects of acetylcholine, whereas M2-receptor antagonism increases the relaxant activity of isoproterenol. Complementary interactions between corticosteroids and long-acting beta2-agonists and between corticosteroids and anticholinergic bronchodilators may be important if these drugs are combined in the treatment of COPD.