Depression is accompanied by an array of neurobiological variations, including altered HPA axis activity, monoamine, growth factor and inflammatory immune functioning. In addition, a recent perspective has entertained the possible role for oxytocin in depressive disorders. Given the involvement of oxytocin in prosocial behaviors such as attachment, affiliation, trust, and social support seeking, it is not surprising this neuropeptide might be involved in the development or maintenance of depressive disorders. This view is supported by evidence that oxytocin interacts with various neuroendocrine, neurotransmitter, and inflammatory processes that have previously been implicated in depression. Thus, it might be profitable to consider the contribution of oxytocin in the context of several neurobiological changes provoked by stressors. The current review examines the relation between oxytocin and depression with a specific focus on the interactions between the oxytocinergic system and stressor-provoked biological and psychosocial responses. The possibility is also considered that oxytocin might increase the salience of social cues, such that positive or negative experiences result in exaggerated responses that may influence affective states.