Recent adoption by the American Conference of Governmental Industrial Hygienists of a Threshold Limit Value of 50 ppm for an 8-hour average exposure to nitrous oxide (N2O) increases the likelihood for its regulation by state and federal occupational health agencies. This review outlines current information on the health risks of N2O inhalation to provide a basis from which safe and reasonably attainable exposure limits can be proposed. Although N2O was for many years believed to have no toxicity other than that associated with its anesthetic action, bone marrow depression in patients administered N2O for extended periods of time and neurological abnormalities in health care workers who inhaled N2O recreationally have disproved this notion. Retrospective surveys of dental and medical personnel have also linked occupational exposure to N2O with a number of health problems and reproductive derangements. Nitrous oxide reacts with the reduced form of vitamin B12, thereby inhibiting the action of methionine synthase, an enzyme that indirectly supports methylation reactions and nucleic acid synthesis. Many, if not all, of the nonanesthetic-related adverse effects of N2O may be ascribed to this action. Animal and human studies indicate that the toxic effects of N2O are concentration- and time-dependent. It is suggested that a time-weighted average of 100 ppm for an 8-hour workday and/or a time-weighted average of 400 ppm per anesthetic administration would provide adequate protection of dental personnel and be achievable with existing pollution control methods.