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Chronic osteomyelitis represents a challenging to treat clinical entity. A case of a whole femur chronic osteomyelitis, definitely treated with total femur resection and a positioning of a modular megaprosthesis in 2 stages is presented. An 81-year-old female, with hip hemiarthroplasty and internal fixation plate of the distal femur presented with signs and symptoms of femur osteomyelitis. Based on the clinical, radiologic and laboratory findings, the diagnosis of chronic femur osteomyelitis was established. Multiple bone cultures from different femur sites revealed the same methicillin resistant S. aureus. The patient was subjected to a two stage femur reconstruction operation. At the first stage, radical debridement, total femur resection and the application of a custom made vancomycin loaded spacer was performed. After a total of 6 weeks i.v. and 3 months oral proper causative antimicrobial treatment a modular megaprosthesis was applied. The patient was definitely treated from total femur chronic osteomyelitis and has returned to her daily activities. Chronic osteomyelitis demands a multidisciplinary approach, including the right causative long-term antimicrobial treatment, as well as the proper surgical treatment, aiming for eradication of infection and best possible postoperative limb function.