Antimicrobials have been fed to livestock for more than 60 years. Veterinarians and producers saw tremendous gains in health and performance, and usage became widespread. Over time, improved management reduced some of the benefit of many feed-through antimicrobials except for a few important diseases. As a result of concerns about antimicrobial resistance, the US FDA restricted the use of medically important antimicrobials. Starting in 2017, medically important antimicrobials were restricted to therapeutic purposes only, and only under the order of a veterinarian. The aim of this review is to provide an overview of commonly used antimicrobials in livestock feed and regulatory changes regarding the veterinary feed directive. When used judiciously, in-feed antimicrobials are an important tool to ensure the health and welfare of food animals while preserving the effectiveness for animals and humans.