We give a brief history and development of the use of analgesic nitrous oxide in various clinical situations, emphasizing the very important difference between analgesic and anesthetic concentrations of the gas. We give evidence for the opioid nature of analgesic nitrous oxide and the probable role that these opioid properties play in its clinical effects. Its uniqueness among the opioids arises from its ability to safely stimulate both mu and kappa opioid receptors thereby modulating these systems, which are at times antagonistic to each other. These opposing systems appear to be particularly important during addictive withdrawal. We also discuss the possible relationship existing between nitric and nitrous oxide.