Glucocorticoids, the adrenal steroids secreted during stress, while critical for successful adaptation to acute physical stressors, can have a variety of deleterious effects if secreted in excess. It has come to be recognized that glucocorticoid excess can have adverse effects in the nervous system, particularly the hippocampus. These effects include disruption of synaptic plasticity, atrophy of dendritic processes, compromising the ability of neurons to survive a variety of coincident insults and, at an extreme, overt neuron death. This review considers the current cellular and molecular bases underlying these adverse glucocorticoid actions, and their relevance to brain aging.