Glucocorticoids (GC) carry out their actions by binding to a specific intracytoplasmic receptor, called the human glucocorticoid receptor (hGR). This receptor belongs to the superfamily of nuclear hormone receptors of ligand-activated transcription factors (5). Their expression is regulated by the NR3C1 gene, which is localized in the short arm of chromosome 5 (5q31.3). This gene gives origin to two highly homologous (6,7) (15)(14). Like all members of and isoforms of the receptor, called this superfamily, hGR in its dimeric state mediates the transactivation of target genes by uniting with specific "glucocorticoid response elements" (GREs) in a promoting region of DNA (26). Its interaction with certain coactivators gives place to one of two mechanisms of gene action: transactivation (induction of gene transcription) or transrepression (repression of gene transcription) (30), thus controlling the expression of genes linked to inflammatory processes, response to stress, glucose homeostasis, and lipid metabolism (5). Moreover, the hGR:GRE complex has other effects such as interacting with NF-KB to block its transcription activity, and avoiding the transcription of cytokines (IL-8), chemokines, cell adhesion molecules (E-selectin), complement factors, and cyclooxygenase-2 (31). The aim of this review is to give an update on these mechanisms and on new GC-mediated effects and the cause of inadequate response to glucocorticoids in specific tissues in disorders such as asthma (22), rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, chronic lymphocytic leukemia, and glucocorticoid-resistant nasal polyps.