The glucocorticoid receptor (GR, or GCR) is a 777-amino acid multidomain nuclear protein which is coded by the NR3C1 (nuclear receptor subfamily 3, group C, member 1) gene at 5q31 which consists of ten exons (1 to 9β). Together with the other steroid receptors progesterone receptor (PR), androgen receptor (AR), the estrogen receptors (ERα and ERβ), and the mineralocorticoid receptor (MR), GR builds the nuclear receptor (NR) superfamily subgroup 3. GR is the receptor for cortisol and other glucocorticoids. It is expressed in most human cell types and regulates the transcription of thousands of genes involved in metabolism, development, stress and inflammatory responses. In the absence of its ligand, GR is bound to heat shock proteins in the cytoplasm. Ligand binding results in GR dislocation to the nucleus, binding to specific glucocorticoid response elements (GREs), recruitment of context specific transcriptional coregulators, and consequently, either activation or repression of the respective target genes. GR coregulators include a large and diverse group of proteins such as histone modifying enzymes, histone acetyltransferases or deacetylases, and many others. GR and glucocorticoids have a critical impact on a very broad spectrum of physiological processes. For example, GR appears to be an important adaptor for endocrine influence – specifically the stress response – on the brain and may play a critical role in psychological disorders such as depression and post-traumatic stress disorder. GR expression also plays a complex role in tumorigenesis which goes beyond its effects on the immune system. In several tumor types, both an oncogenic and a tumor suppressive function of GR has been found depending on specific tumor conditions.