Antimicrobials in human medicine are classified by The World Health Organization (WHO) into three groups: critically important antimicrobials (CIA), highly important antimicrobials (HIA), and important antimicrobials (IA). CIA are antibiotic classes that satisfy two main criteria: that they are the sole or the only available limited therapeutic option to effectively treat severe bacterial infections in humans (Criterion 1), and infections where bacteria are transmitted to humans from non-human sources or have the potential to acquire resistance genes from non-human sources (Criterion 2). WHO emphasizes the need for cautious and responsible use of the CIA to mitigate risk and safeguard human health. Specific antimicrobials within the CIA with a high priority for management are reclassified as “highest priority critically important antimicrobials (HP-CIA)” and include the 3rd generation of cephalosporins and the next generation of macrolides, quinolones, glycopeptides, and polymyxins. The CIA list is the scientific basis for risk assessment and risk management policies that warrant using antimicrobials to reduce antimicrobial resistance in several countries. In addition, the CIA list ensures food safety in the food industry, including for the popular food chain companies McDonald's and KFC. The continuous update of the CIA list reflects the advancement in research and emerging future challenges. Thus, active and deliberate evaluation of antimicrobial resistance and the construction of a list that reflects the specific circumstances of a country are essential to safeguarding food security.