Ketamine is an N-methyl-d-aspartate non-competitive receptor antagonist that acts as an analgesic agent and has notable use in anesthesia, psychiatry, and pain management, among other disease states. N-methyl-d-aspartate amplifies pain signals, the development of central sensitization, and opioid tolerance. Non-surgical patients who have high opioid dependence and concomitant chronic conditions such as sickle cell disease have also been studied and may benefit from the use of ketamine in pain exacerbation. Ketamine has been found to improve analgesia in both adults and children, while reducing the need for opioids. Traditionally, ketamine is administered as intravenous or intramuscular. Parenteral ketamine can be used as a sole agent to manage acute pain or as a multimodal approach to pain management in combination with an opioid. Intranasal ketamine utilizes the nasal mucosa to bypass first-pass metabolism and the blood-brain barrier to ultimately be absorbed in the brain by olfactory sheets.