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Antidepressant drugs are a mainstay in psychiatric treatment and have the ability to influence neural substrates related to social bonding and interaction. This article explores the potential neurobiological overlap between social attachment and antidepressant mechanisms and reviews work related to the effects of antidepressants on separation distress, social affiliation, dominance hierarchies, romantic love, and socio-emotional processing. It is proposed that similarities between antidepressant pharmacology and the neurobiological effects of an effective care-giver may help create a sense of safety that in turn promotes changes in behavior and mood.