Pain is a ubiquitously unpleasant feeling among humans as well as many animal species often caused by actual and potential tissue damage. However, it is absolutely crucial for our survival in many ways. Acute pain can signal the presence of danger or life-threatenting events, which help escape noxious stimuli. By contrast, when pain becomes chronic or persistent, it becomes an encumbrance and exerts deleterious effects to the body and mind, often co-occured with anxiety and depression. Additionaly, chronic pain is more or less an economic burden for the patients because it requires immediate medical treatments and seriously hinders pepople in their work. To date, there has been a lack of breakthrough progress in the pain field, despite huge gains in basic science knowledge obtained using animal models, it is still difficult to develop many new clinically effective analgesic drugs to control pain with long-term effectiveness. Opioids and nonsteroidal anti-inflammatory drugs were introduced for pain management more than a century ago. Those drugs do have proven efficacy in the treatment of pain but the use of them are also significantly limited due to the multiple serious adverse effects (e.g., drug resistance, addiction and gastrointestinal bleeding). In the field of pain relief and treatment, there is a strong impetus to develop and establish novel analgesics that must be safer and more effective to offer significant pain relief for a wide variety of painful conditions. Preliminary evidence suggests that oxytocin might be the ideal candidate as a target for reducing the severity of pain. In this review, we present a summary of the total literature related to the effects of oxytocin on pain modulation in both animals and humans. Better understanding the fundamental physiopharmacology of the actions of oxytocin in pain may highlight novel mechanisms associated with analgesia.