Nitrous oxide (N2O) is the nearly ‘ideal’ clinical sedative. For Pediatric Dentistry is almost as important as local anesthesia. Many children (as well as children with special needs) would have been obliged to undergo Deep Sedation or General Anesthesia if it wasn’t available. N2O has been used for well over 150 years in clinical dentistry for its analgesic and anxiolytic properties. In this chapter the way is being used in Dentistry will be discussed. This small and simple inorganic chemical molecule has simultaneous effects of analgesia, anxiolysis, and anesthesia that are of great clinical interest. Recent studies have helped to clarify the analgesic mechanisms of N2O but the mechanisms involved in its anxiolytic and anesthetic actions remain less clear. Research indicates that the analgesic effect of N2O is opioid in nature, while the anxiolytic effect, resembles that of benzodiazepines and may be initiated at selected subunits of the -aminobutyric acid type A (GABAA) receptor. Similarly, the anesthetic effect of N2O may involve actions at GABAA receptors and possibly at N-methyl-D-aspartate receptors as well.