Non-typhoidal Salmonella is the primary foodborne zoonotic agent of salmonellosis in many countries. Non-typhoidal Salmonella infections are transmited to humans primarily through consumption of contaminated foods from animal origin, whereas S. Typhi and Paratyphi infections are spread directly or indirectly by contact with an infected person. Quinolones exhibit potent antibacterial activity against Salmonella and are usually the irst choice of treatment for life-threatening salmonellosis due to multidrugresistant strains. However, by the early 1990s, quinolones have been approved for use in food-producing animals. The increased use of this group of antimicrobials in animal has led to the concomitant emergence of quinolone-resistant non-typhoidal Salmonella strains. However, in some countries, there are no legal provisions, which apply to veterinary drugs. This situation provides favorable conditions for spread and persistence of quinolone-resistant bacteria in food-producing animals. The objective of this chapter is to review the current regulatory controls for the use of quinolones in food-producing animals, its efect on development of quinolone resistance, and the potential impact on human and animal health. Moreover, this chapter reviews the current knowledge of quinolone resistance mechanisms and the future directions of research with particular atention to the strategies to control the emergence of quinolone-resistant Salmonella.