Glucocorticoids (GCs), produced by the stress-responsivehypothalamic–pituitary–adrenal axis, are well recognized for their regulatory role inperipheral metabolism. GCs are also known to regulate various brain functions, withwell-described effects on human cognition. Increased GC exposure in humans—includingexposure to the endogenous GC, cortisol—at levels associated with stress, decreasesmemory and learning function. These results extend evidence from in vitro studies of synaptic andcell function and evidence from animals indicating the GCs can regulate substrates of memoryfunction. While considerable evidence details these effects in adult humans and animals, relativelyless is know about the effect of GCs on cognitive function in children and older adults.Investigators have suggested that children, particularly preschool-aged children, may bevulnerable to adverse consequences of increased GC secretion resulting from stress andneuropsychiatric diseases such as depression. Adverse GC effects on memory substrates andmemory function in the adult have also fostered concern that age-related changes, includingchanges in GC receptors and changes in circulating cortisol levels, could lead to age-relatedincreases in the adverse effect of GCs on brain function. Investigators have reported anassociation between age-related increases in cortisol levels and age-related memory decline, butthis association may or may not be due to a direct effect of cortisol on memory substrates. Anumber of possible treatment approaches to prevent or remediate adverse GC-induced effects areunder development. In general, the use of safe and effective agents for blocking adverse GCeffects on brain functions including memory may offer benefits to individuals suffering acute andchronic stressors and could prevent brain changes relevant to stress, aging, and stress-relatedneuropsychiatric diseases.