Glucocorticoids have significant anti-inflammatory effects and are widely used in the treatment of chronic airway inflammatory diseases (including allergic rhinitis, chronic rhinosinusitis, asthma, chronic obstructive pulmonary disease, etc.). Glucocorticoids can bind to the glucocorticoid receptors (GR) in the nucleus, pass through the nuclear pores, and then exert physiological effects by regulating the expression of related genes in the nucleus. However, some patients with long-term use of glucocorticoids have poor efficacy or even ineffectiveness, that is, corticosteroid resistance (CR) phenomenon. CR affects the therapeutic effect of glucocorticoids, leading to the persistence of inflammatory state. Therefore, understanding the mechanism of CR is crucial for guiding the treatment of such diseases. The mechanisms of CR in different types of chronic airway inflammatory diseases are similar to some extent. In recent years, studies have suggested that the occurrence of CR is closely related to the changes of GR (such as gene expression, affinity, gene polymorphism, etc.). In this article, we briefly review the therapeutic mechanism of glucocorticoids and summarize the research progress of receptor-related CR mechanism.