Stress is a potent modulator of brain and cognitive function. Depending on the circumstances, stress can either facilitate or impair memory processes. Our research aims to unravel how neurobiological mechanisms related to learning and plasticity are affected by stress conditions leading to opposite effects on memory function (facilitating vs. impairing). By focusing on key plasticity-related proteins, we investigate the mechanisms that translate stress’ actions into such diverse cognitive outcomes. Our work has implicated the neural cell adhesion molecules of the immunoglobulin superfamily, NCAM and L1, on the effects of stress on brain and cognitive function (Sandi, 2004; Sandi & Touyarot, 2006). In the hippocampus, memory-facilitating and memory-impairing stress conditions lead to opposite patterns of expression of cell adhesion molecules (Sandi et al. 2005; Venero et al. 2006), which underscore these molecules as potential mediators of the cognitive effects of stress. Although glucocorticoid treatments do not reproduce exactly the changes on plasticity-related proteins induced by stress, available evidence indicates that these steroid hormones play a major role on stress-induced modulation of both cell adhesion molecules, and other plasticity-related proteins. These findings (1) have implications to understand stress in the context of both pathology and adaptation, and (2) underscore cell adhesion molecules as potential therapeutic targets in stress-related cognitive disturbances (Cambon et al. 2004).