This review considers the current position of nitrous oxide in anaesthetic practice and balances potential beneficial and disadvantageous effects. The classic adverse characteristics of nitrous oxide, such as diffusion hypoxia, expansion of gas-filled spaces, and postoperative nausea and vomiting, are often cited as reasons to avoid this old drug. Recent concerns regarding neurotoxicity, adverse cardiovascular outcomes, and wound complications have further hardened many practitioners against nitrous oxide. New evidence and underpinning mechanistic data, however, suggest potential beneficial effects on the central nervous system, cardiovascular system, and acute and chronic pain. While we await the outcome of large studies including ENIGMA-II, many clinicians have already decided against this agent. The authors argue that this abandonment may be premature. Clinical Trial Registration None required.