Nalbuphine is a potent opioid analgesic that is not under the Controlled Substance Act (CSA). It exhibits agonistic effects on kappa and antagonistic on mu-receptors, which explains its unique pharmacodynamic properties of combining equal to morphine analgesic efficacy with favourable side effects profile. Nalbuphine has been widely used to treat acute, perioperative, and chronic pain since the 1980. Nalbuphine is available as a parenteral solution only; oral forms do not use due to poor oral bioavailability (about 15%) caused by extensive presystemic metabolism. The sole availability of injectable nalbuphine medications drastically limits the utilization of this non-scheduled potent opioid analgesic with a wide therapeutic window and low incidence of side effects outside the clinical settings. Considering the need for practical medicine in non-injectable nalbuphine preparations bypassing the hepatic first-pass effect, several clinical trials with rectal and nasal nalbuphine administration were conducted for the present day. Here we review the results of relevant pharmacokinetic and clinical studies, focusing on recently published data comparing the pharmacokinetic parameters of developed nalbuphine nasal spray with intravenous and intramuscular injections of nalbuphine solution in healthy volunteers. Challenges in nalbuphine nasal form development are briefly discussed as well.