Early history: Evidence of osteomyelitis dates back to more than 250 million years ago in the fractured spine of dimetrodon Permian reptile. From the time of Hippocrates (460–370 BC), infection after fracture of the bone has been reported, although the clinical aspects of these post fracture infections were reported much later. Pathology: Nelaton coined the term “osteomyelitis,” describing it as inflammation of the bone caused by an infectious agent. It can be due to trauma, surgery, or secondary to any vascular insufficiency. The cause of osteomyelitis remained obscure until Louis Pasteur described the causative agents for infection. Evolution of treatment: Early treatment consisted of a combination of conservative and radical approaches in the form of excision and immobilization primarily. 1948 a paper from the Royal Hospital for Sick children in Glasgow first illustrated the benefits of penicillin in osteomyelitis. In 1980, the introduction of Fluoroquinolones revolutionized the treatment for infective cases. Rowling et al. by 1959 reported a positive approach to treat chronic osteomyelitis, requiring surgery to improve the blood supply over the scarred and affected bone. The involved bone requires excision of the affected soft tissue and scarring to improve recovery for adequate delivery of antibiotics over the bone that is chronically affected. Conclusion: The management principles like extensive debridement, dead space management, and antibiotic therapy still hold true in current times. The introduction of antibiotics revolutionized the treatment strategy leading to the transition from a highly fatal condition to a treatable disease.