Background and objectives: due to the neurotoxic effect caused by high levels of cortisol, studies suggest that stress and certain psychiatric disorders, such as mood disorders, have influences under the hippocampus, causing a decrease in volume and consequent memory changes. This study aims to evaluate the relationship between hippocampal volume in patients with mood disorders under therapy. Materials and Methods: the PRISMA protocol for systematic reviews was followed. Pubmed, Cochraine and Scielo databases were searched by terms “Hippocampus”, “Mood Disorders” and “MRI”, and variants in other languages, in human, from January 2011 to September 2016. The individual quality of the articles was analyzed using the Cochraine modified scale for clinical trials and the Agency for Healthcare Research and Quality scale for observational studies. Results: all studies showed reduction of hippocampal volume in depressive patients. Change in hippocampal volume is not related to the use of antidepressant. Particularly the sub-region of the subculum is more reduced, without lateralizations. Significant relationship between stress and right hippocampal reduction. The findings seem to point out: a common pathway of hippocampus reduction, mediated by stress, explaining memory deficits due to depression, where the cortisol pathway seems to act; alteration in the prefrontal cortex; reduction in the subiculum related to inhibition of the hypothalamic-pituitary-adrenal axis, corroborating the hypothesis of cortisol. Conclusions: the papers suggest: association between global hippocampal atrophy with mood disorders; reduction of hippocampal subiculum; refractoriness to clinical treatment among patients with lower hippocampal volume.