Bone infection as one of the most challenging diseases in orthopedics, is characterized by a prolonged treatment and a high recurrence rate, imposing a significant disease burden on both patients and society. With the continuous emergence of drug-resistant bacteria and a deepening understanding of biofilm theory, traditional single-modality treatment have become inadequate in addressing these complex clinical challenges. This paper provides an in-depth analysis of the century-long dilemma in the treatment of bone infections. Through systematic theory, it shares the author’s “Chongqing experiences” in bone infection management—a systematic strategy proposed based on extensive clinical practice and theoretical summarization. This approach emphasizes the importance of multi-disciplinary treatment, staged treatment, precise debridement, and a comprehensive grasp of the principles underlying bone infection therapy. The article also discusses humanistic considerations and future prospects in the treatment of bone infections, aiming to offer practical and valuable basis for clinical management.