Hyper-saline habitats (waters with salinity >35 ppt) are among the harshest aquatic environments. Relatively few species of teleost fish can tolerate salinities much above 50 ppt, because of the challenges to osmoregulation, but those that do, usually estuarine, euryhaline species, show a strong ability to osmoregulate in salinities well over 100 ppt. Typically, plasma Na(+) and Cl(-) concentrations rise slowly or not at all up to about 65 ppt. At higher salinities ion levels do rise, but the increase is small relative to the magnitude of increase in concentrations of the surrounding water. A number of adjustments are responsible for such strong osmoregulation. Reduced branchial water permeability is indicated by the observation that with the exposure to hyper-salinities drinking rates rise more slowly than the branchial osmotic gradient. Lower water permeability limits osmotic water loss and greatly reduces the salt load incurred in replacing it. Still, increased gut Na(+)/K(+)-ATPase (NAK) activity is necessary to absorb the larger gut salt load and increased HCO(3) (-) secretion is required to precipitate Ca(2+) and some Mg(2+) in the imbibed water to facilitate water absorption. All Na(+) and Cl(-) taken up must be excreted and increased branchial salt excreting capacity is indicated by elevated mitochondrion-rich cell density and size, gill NAK activity and expression of chloride channels. Excretion of Na(+) and Cl(-) occurs against a larger gradient than in seawater and calculation of the equilibrium potential for Na(+) across the gill epithelium indicates that the trans-epithelial potential required for excretion of Na(+) climbs with salinity up to about 65 ppt before leveling off due to the increasing plasma Na(+) levels. During acute transition to SW or mildly hyper-saline waters, some species have shown the ability to upregulate branchial NAK activity rapidly and this may play an important role in limiting disturbances at higher salinities. It does not appear that the opercular epithelium, which in SW acts in a way that is functionally similar to the gills, continues to do so in hyper-saline waters. Little is know about the hormones involved in acclimation to hyper-salinity, but the few studies available suggest a role for cortisol, but not growth hormone and insulin-like growth factor. Despite the increased transport capacity evident in both the gill and gut in hyper-saline waters there is no clear trend toward increased metabolic rate. These studies provide a general outline of the mechanisms of osmoregulation in these species, but significant questions still remain.