The hypothalamic neuropeptide oxytocin (OT) is well known for its prosocial, anxiolytic, and ameliorating effects on various psychiatric conditions, including alcohol use disorder (AUD). In this chapter, we will first introduce the basic neurophysiology of the OT system and its interaction with other neuromodulatory and neurotransmitter systems in the brain. Next, we provide an overview over the current state of research examining the effects of acute and chronic alcohol exposure on the OT system as well as the effects of OT system manipulation on alcohol-related behaviors in rodents and humans. In rodent models of AUD, OT has been repeatedly shown to reduce ethanol consumption, particularly in models of acute alcohol exposure. In humans however, the results of OT administration on alcohol-related behaviors are promising but not yet conclusive. Therefore, we further discuss several physiological and methodological limitations to the effective application of OT in the clinic and how they may be mitigated by the application of synthetic OT receptor (OTR) agonists. Finally, we discuss the potential efficacy of cutting-edge pharmacology and gene therapies designed to specifically enhance endogenous OT release and thereby rescue deficient expression of OT in the brains of patients with severe forms of AUD and other incurable mental disorders.