The US Food and Drug Administration (FDA) new animal drug approval process evaluates veterinary drugs intended for use in food-producing animals for safety and effectiveness. As part of the human food safety evaluation, new animal drugs are evaluated for microbial food safety, toxicology and residue chemistry. The chapter summarizes the evaluation process that includes the assignment of tolerance(s), withdrawal periods and milk discard times. It also establishes the criteria for violative residues, that is, residues above the established tolerance limits which may have potential adverse health effects in humans.