For decades, it was widely assumed that glucocorticoids (GCs) work solely through changes in gene expression to exert their physiological actions, a process that normally takes several hours to occur. However, recent evidence indicates that GCs might also act at the membrane through specific receptors to exert multiple rapid effects on various tissues and cells. GCs modulate hormone secretion, neuronal excitability, behavior, cell morphology, carbohydrate metabolism and other processes within seconds or minutes. These early actions occur independent of the genome and are transduced by the same biochemical effector pathways responsible for mediating rapid responses to neurotransmitters. The biological significance of most rapid GC effects are not well understood, but many might be related to the important functions that this hormone plays in modulating stress responses.