Glucocorticoids exert a multiplicity of effects, yet all these effects appear to be mediated by the product of a single gene – the glucocorticoid receptor (GR). As the human genome has proved to consist of fewer genes than expected, attention has turned to variant forms of gene products as a source of increased proteome size and complexity of regulatory signalling networks. Expression of the human GR is regulated by at least three distinct promoters (1A, 1B and 1C) that regulate transcription of mRNA species incorporating different exon 1 sequences. Promoters 1B and 1C regulate expression of mRNA species that are detected in most tissues, while promoter 1A functions selectively in haematopoietic cells. Alternative splicing of GR exons is known to produce several variants, although exon 1 is non-coding so that the different promoters do not encode distinct proteins. Alternative splicing of the eight coding exons is well established, however. The most extensively studied splice variant, GR beta, results from usage of a different exon 9 to that used in the `classic’ (GR alpha) form (1). The GR beta variant, which cannot bind ligand, may exert a dominant-negative effect on glucocorticoid signalling and a number of reports suggest that aberrant expression is linked to disease. Controversy continues to surround the likely significance of this variant, however, particularly with regard to its apparently low level of expression. Other splice variants include GR-P (alternatively known as GR delta), which lacks exons eight and nine (2), and a group of exon 2 splice variants (3). We are currently studying an evolutionarily conserved splice variant, GR gamma, that utilises the first three bases of the intron separating exons three and four to code for an additional arginine that is located in the DNA binding domain of the receptor (4). An additional level of complexity in GR variants is introduced by the reported use of alternative initiating codons (5) which leads to isoforms with different amino-termini, each of which may regulate both a common and a unique set of genes. Although a unique function has not yet been definitively assigned to any of these variants, the important possibility arises that some or all of them could fulfill distinct functions, perhaps providing a route to pharmacological modulation of signalling through different pathways.