We review here that oxytocin (OT) is released into blood and within distinct brain regions in response to stressful and social stimuli, and has been shown to have an antidepressant-like effect in animal studies. Clinical reports suggest OT to be a promising drug for psychiatric diseases such as depression, anxiety disorders, schizophrenia, and autism. OT may also have therapeutic potential in the treatment of major depressive disorders, even though OT administered into blood does not readily cross the blood-brain barrier. Physiological functions such as sexual activity and mating induce the release of OT in the central nervous system. A drug for the treatment of sexual dysfunction, sildenafil, enhances the electrically evoked release of OT from the posterior pituitary. This drug has antidepressant-like effects through activation of an OT signaling pathway. These results suggest that sildenafil may have promise as a potential antidepressant.