Structural and morphological changes in limbic brain regions are associated with depression, chronic stress and antidepressant treatment, and increasing evidence supports the hypothesis that dysregulation of cell proliferation contributes to these effects. We review the morphological alterations observed in two brain regions implicated in mood disorders, the prefrontal cortex and hippocampus, and discuss the similarities and differences of the cellular consequences of chronic stress. We briefly discuss the proposed mechanisms implicated in neuroplasticity impairments that result from stress and that contribute to mood disorders, with a particular interest in adult neurogenesis and gliogenesis. This information has contributed to novel antidepressant medication development that utilizes adult neurogenesis and gliogenesis as preclinical cellular markers for predicting antidepressant properties of novel compounds.