Nitrous oxide (N2O, laughing gas) was first discovered by the English scientist Joseph Priestly and has been used for more than 150 years. It has remained one of the most widely used anesthetics in both dental and medical applications. This small and simple inorganic chemical molecule has indisputable effects of analgesia, anxiolysis, and anesthesia that are of great clinical interest. As a general anesthetic, it is very weak and is generally not used as a single agent. It may be used as a carrier gas with oxygen in combination with more potent general inhalational gases for surgical anesthesia. In dentistry, it is commonly used as a single agent (with oxygen) for partial sedation, most commonly in pediatric dental populations. Findings to date indicate that the analgesic effect of N2O is opioid in nature, and, like morphine, may involve a myriad of neuromodulators in the spinal cord. The anxiolytic effect of N2O, on the other hand, resembles that of benzodiazepines and may be initiated at selected subunits of the gamma-aminobutyric acid type A (GABA(A)) receptor. Similarly, the anesthetic effect of N2O may involve actions at GABA(A) receptors and possibly at N-methyl-D-aspartate receptors as well.