The equine industry holds substantial economic importance not only in the USA but worldwide. The occurrence of various infectious bacterial diseases in horses can lead to severe health issues, economic losses, and restrictions on horse movement and trade. Effective management and control of these diseases are therefore crucial for the growth and sustainability of the equine industry. While antibiotics constitute the primary treatment strategy for any bacterial infections in horses, developing resistance to clinically important antibiotics poses significant challenges to equine health and welfare. The adverse effects of antimicrobial overuse and the escalating threat of resistance underscore the critical importance of antimicrobial stewardship within the equine industry. There is limited information on the epidemiology of antimicrobial-resistant bacterial infections in horses. In this comprehensive review, we focus on the history and types of antimicrobials used in horses and provide recommendations for combating drug-resistant bacterial infections in horses. This review also highlights the epidemiology of antimicrobial resistance (AMR) in horses, emphasizing the public health significance and transmission dynamics between horses and other animals within a One Health framework. By fostering responsible practices and innovative control measures, we can better help the equine industry combat the pressing threat of AMR and thus safeguard equine as well as public health.