Basal ray-finned fish (Actinopterygii) possess a single glucocorticoid receptor (GR) and when compared to the lobe-finned vertebrate (Sarcoptergyii) GR possess nine additional amino acids between the zinc-finger of the DNA binding domain. A whole genome duplication event which occurred between 320-350 MYA in the teleost lineage following the split from the basal ray-finned fish resulted in 2 GRs: one GR group, GR1, has retained the 9 amino acids insert whereas the other group, GR2, has not. The exception to this is the zebrafish, that have lost one of the GRs, but they do possess 2 GRs with a splice variant that lacks the C-terminal portion of the GR to form GRβ which acts as a dominant-repressor of the wildtype GR. Another splice variant sees the basal ray-finned GR and teleost GR1 without the 9 amino acids insert. The molecular basis for GRs retention is beginning to be unravelled. In Pantadon buchholzi, rainbow trout, carp, marine and Japanese medaka GR2 is more sensitive to glucocorticoids (GC), thus potentially playing a more significant role in regulating gene expression at basal circulatory GC concentrations. However, this division in GC sensitivity is not seen in other species. The few studies to evaluate the significance of the 9 amino acid insert have shown that it affect maximal transactivational activity the extent to which is dependent on the number of glucocorticoid response elements (GREs) present in the reporter plasmid. The retention of these GRs would suggest there was an evolutionary advantage, which saw the development of a complex regulatory process to mediate the actions of the glucocorticoids.