Direct food additives can be broadly defined as substances that are intentionally added to food or beverages during preparation or storage to achieve a particular technical effect within the food. In contrast, processing aids are used to facilitate food processing only and are not intended to alter the characteristics of the food itself. In this chapter, the regulations, definitions, and approval processes for food additives and processing aids are reviewed for the following specific countries/jurisdictions: Argentina, Australia, Brazil, Canada, China, the European Union, Japan, New Zealand, and the United States. Although there are some differences, all have regulations that require an evaluation before market approval to ensure that the food containing the additives is safe for the entire population. A positive list of approved food additives is publicly available in all jurisdictions, with some exceptions for the United States. The safety assessment principles applied during evaluation are based on principles developed by the Joint FAO/WHO Expert Committee on Food Additives, which are described. Future challenges include developing an understanding of the appropriate application of non-animal toxicology testing alternatives into safety assessments, addressing emerging concerns such as potential effects on the microbiome, continued efforts to harmonize global regulations, and addressing consumer concerns to promote optimal use of limited food supplies for a growing global population.