Antimicrobial resistance (AMR) represents a global threat to both human and animal health and has received increasing attention over the years from different stakeholders. Certain AMR bacteria circulate between humans, animals, and the environment, while AMR genes can be found in all ecosystems. The aim of the present review was to provide an overview of antimicrobial use in food-producing animals and to document the current status of the role of farm animals in the spread of AMR to humans. The available body of scientific evidence supported the notion that restricted use of antimicrobials in farm animals was effective in reducing AMR in livestock and, in some cases, in humans. However, most recent studies have reported that livestock have little contribution to the acquisition of AMR bacteria and/or AMR genes by humans. Overall, strategies applied on farms that target the reduction of all antimicrobials are recommended, as these are apparently associated with notable reduction in AMR (avoiding co-resistance between antimicrobials). The interconnection between human and animal health as well as the environment requires the acceleration of the implementation of the ‘One Health’ approach to effectively fight AMR while preserving the effectiveness of antimicrobials.