Osteomyelitis, a severe and debilitating bone infection, presents a significant challenge in healthcare due to its intricate management requirements. This chapter explores the evolution of orthoplastic surgical approaches toward managing osteomyelitis, encompassing both microsurgical and non-microsurgical interventions. Through a comprehensive review of literature, case studies, and expert insights, this chapter aims to bridge the theoretical knowledge-practice gap, offering nuanced perspectives on addressing incapacitating bone infections. The integration of microsurgery has revolutionized osteomyelitis treatment by providing precision and flexibility in reconstructive options. Techniques such as vascularized bone grafts, free flaps, and composite tissue transfers not only eradicate infection but also restore form and function. The selection criteria, surgical techniques, and outcomes associated with these advanced procedures are discussed in detail. Furthermore, this chapter delves into the underlying etiology, diagnostic modalities, and antimicrobial therapies essential for successful treatment planning. Non-microsurgical approaches, including local and regional flaps, antibiotic-impregnated bone cement, and bioengineered scaffolds, offer viable alternatives in certain clinical scenarios. Despite advancements, challenges persist, particularly concerning wound management and implant-related infections. This chapter emphasizes the importance of appropriate antibiotic therapy and surgical debridement in treating osteomyelitis, especially those involving implants. The reconstructive ladder provides a guide for varying degrees of open wound interventions, with modern techniques like Negative Pressure Wound Therapy with Instillation and Dwell Time (NPWTi-d) enhancing flexibility and efficacy in wound closure. In conclusion, this chapter provides a comprehensive overview of plastic surgical interventions for osteomyelitis, highlighting the need for a multidisciplinary approach and continual innovation to address this complex and evolving pathology.