Orthopedic implant-related infections (OIRIs), including prosthetic joint infections (PJIs), pose significant challenges for orthopedic surgeons and patients alike, highlighting the critical need for effective infection prevention strategies. With incidence rates of PJIs reaching up to 20% following septic revisions and 30% for open fractures, the burden of OIRIs is both medically and economically substantial, costing over $1.62 billion in 2020 alone. The evolution of antimicrobial coatings has emerged as a pivotal approach in combating these infections. This chapter explores the historical development of orthopedic implants and infection control strategies, emphasizing the mechanisms behind antimicrobial coatings that enhance biocompatibility and durability while effectively preventing bacterial colonization. While traditional antibiotic prophylaxis has significantly reduced surgical site infections, the risk of infection remains, particularly in the presence of foreign materials such as implants. Novel coating technologies, including smart and synergistic multi-mechanism approaches, hold promise for future advancements in infection control. However, the challenges of regulatory considerations and balancing efficacy with biocompatibility must be addressed. This comprehensive examination underscores the importance of innovative solutions in the fight against OIRIs, aiming to improve patient outcomes and reduce healthcare costs. Ultimately, the integration of advanced antimicrobial coatings into orthopedic surgery represents a critical frontier in enhancing the safety and longevity of orthopedic implants.