Stress may lead animal and human behavior to an unstable condition in short and long term. It is a risk factor to a mental disorder such as depression, which is generally related to a failure after an effort. Its high prevalence is worldwide and it is a WHO (World Health Organization) concern. Depression may impair social, economical and affective relationships, besides bringing great suffering to the human being. The main symptoms are decreased energy and motivation, anhedonia, sadness, difficulty for concentration and memory, bonding disruptions, etc. The most accepted hypothesis for depression can be well recognized by the main drugs currently adopted for its treatment: they include serotonin and noradrenaline as their fundamental basis. However, their efficacies are still limited. A promising candidate that might help modulate this disease is oxytocin (OT). OT is a nonapeptide produced by the hypothalamus which exerts central and peripheral effects, not only during pregnancy and lactation, but acts in male and non pregnant females as well. It is being considered as an antistress neuropeptide and it has antidepressive effects. However, the blood brain barrier greatly impairs peripheral OT to reach the brain. The general goal of this review is to raise some issues concerning advantages and difficulties related to a possible exogenous administration of OT for this mental disorder. More specifically, it will be reviewed: 1. stimuli for OT release (behavioral/ endocrinological and chemical/drugs); 2. OT effects on the central nervous system, mainly related to stress; 3. exogenous OT: routes of administration, blood brain barrier, indirect mechanisms of action, whole molecule x fragments of OT, doses. This review will not cover all aspects of the multifactorial disorder such as depression into all its variables. However, it may contribute to the understanding of one possible component, the oxytocinergic system.