Nalbuphine has been commercially available for 40 years for the treatment of acute pain; few studies have centered on management of chronic pain. Nalbuphine unique pharmacology is an advantage in pain management. It is µ antagonist, partial κ agonist for G-proteins and beta-arrestin-2. Benefits are related to G-protein interactions resulting in less nausea, pruritus, and respiratory depression than morphine. At low doses, nalbuphine reduces side effects particularly respiratory depression without loss of analgesia when combined with potent opioids. Nalbuphine pharmacokinetics are moderately altered in renal failure. Several studies have found that nalbuphine reduces uremic pruritus. Nalbuphine has drawbacks: it is not an oral formulation, it causes withdrawal in patients on sustained released opioids, and it cannot be used to treat an opioid withdrawal syndrome. Nalbuphine, despite being a µ receptor antagonist produces a drug-liking effect and can be abused. There are very few deaths associated with nalbuphine alone in part due to the fact it is rarely used but also related to a ceiling on respiratory depression.