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Domain structure of the receptor polypeptide and association with accessory proteins: This review summarizes our present knowledge on the different forms of the glucocorticoid receptor emphasizing structure and functional significance. The nonactivated receptor resides in the cytoplasm. It contains the human receptor polypeptide of 777 amino acids as heteromeric complex in association with two molecules of the heat-shock protein hsp90 and one immunophilin. After binding the hormonal ligand, the receptor becomes activated by dissociation of these accessory proteins. The receptor functions as transcriptional regulator: The receptor polypeptide itself, complexed with hormone, moves on into the cell nucleus to there interact with chromatin and to affect transcriptional processes. By binding as homodimer to specific response elements on the DNA, the receptor functions as positive transcription factor causing increased expression of tissue-specific genes. Alternatively, the receptor interacts with transcription factors like AP-1 or NF-kappaB and inhibits their effects on actively transcribed genes. Pharmacological considerations: The pharmacological possibilities of influencing the diverse medical actions of glucocorticoids are discussed on the level of receptors.