The balance in actions mediated by mineralocorticoid (MR) and glucocorticoid (GR) receptors in certain regions of the brain, predominantly in the limbic system, appears critical for neuronal activity, stress responsiveness, and behavioral programming and adaptation. Alterations in the MR/GR balance appear to make nervous tissue vulnerable to damage; such damage can have adverse effects on the regulation of the stress response and may increase the risk for psychopathology. Besides the hippocampal formation, other subpopulations of neurons in extra-hippocampal brain areas have been also shown recently to be sensitive to changes in the corticosteroid milieu. From a critical analysis of the available data, the picture that emerges is that the balance (or imbalance) between MR/GR activation influences not only cell birth and death, but also other forms of neuroplasticity. MR occupation appears to promote pro-survival actions, while exclusive GR activation favors neurodegeneration. Interestingly, the sustained co-activation of both receptors, for example in chronic stress conditions, usually results in less drastic effects, restricted to dendritic atrophy and impaired synaptic plasticity. As our knowledge of the plastic changes underpinning the wide spectrum of behavior effects triggered by corticosteroids/stress growths, researchers should be able to better define new targets for therapeutic intervention in stress-related disorders.