Corticosteroid hormones are released in high amounts after stress. The hormones enter the brain compartment and bind to high affinity mineralocorticoid receptors--particularly enriched in limbic regions--as well as to lower affinity glucocorticoid receptors which are more ubiquitous. Shortly after the stressful event, corticosteroids (in concert with specific monoamines and neuropeptides) have the potential to increase cellular excitability in subfields of the hippocampus, like the CA1 area. These effects are rapid in onset and occur via a nongenomic pathway. At the same time, however, the hormones also start slower, gene-mediated processes. These cause attenuation of excitatory information flow through the CA1 hippocampal area. Induction of long-term potentiation at that time is impaired. This may help to normalize hippocampal activity some hours after the stressful event and preserve information encoded within the context of the event. These adaptational effects of the hormones may become maladaptive if the stressful event is associated with other challenges of the network (like ischemic insults) or when stress occurs repetitively, in an uncontrollable and unpredictable manner. In that case, i) normalization of activity seems to be less efficient (particularly when other limbic areas like the amygdala nuclei are activated during stress), ii) induction of long-term potentiation is hampered at all times and iii) serotonin responses are attenuated. This may contribute to the precipitation of clinical symptoms in stress-related disorders such as major depression. A better understanding of the corticosteroid actions could lead to a more rational treatment strategy of stress-related disorders.