Chronic osteomyelitis (COM) represents a progressive inflammatory process that lasts at least 6 weeks and is caused by microbes, leading to bone destruction, necrosis, and sequestrum formation. The hallmark of the pathogenesis of chronic osteomyelitis is the formation of the biofilm [1, 2]. Diagnosis of chronic osteomyelitis is based on the patient history, clinical presentation, laboratory test, radiological findings, and biopsy. Biopsy/culture remains the gold standard for diagnosis of chronic osteomyelitis. Many classifications have been proposed for COM. Cierny-Mader’s classification proved most useful for clinical management and research in chronic osteomyelitis. Despite the recent advances in science and technology, managing chronic osteomyelitis remains very challenging. Successful treatment of the COM encompassed careful appreciation and medical optimization of the host physiological status, appropriate systemic antibiotic therapy, extensive surgical debridement to remove biofilm and all substrate attachment plus local antibiotic depot, and reconstruction of the bone and soft tissue defect due to debridement. Multidisciplinary collaboration is necessary for the delivery of optimal clinical outcomes.