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Bacterial osteomyelitis causes substantial morbidity worldwide, despite continued progress toward understanding its pathophysiology and optimal management. The approach to osteomyelitis depends upon the route by which bacteria gained access to bone, bacterial virulence, local and systemic host immune factors, and patient age. While imaging studies and nonspecific blood tests may suggest the diagnosis, an invasive technique is generally required to identify the causative pathogens. Given the paucity of comparative clinical trials, antibacterial regimen selection has been largely guided by knowledge of the relative activities and pharmacokinetics of individual drugs, supported by data from animal models. Definitive therapy often requires a combined medical and surgical approach. Newer microvascular and distraction osteogenesis techniques and the use of laser doppler allow more complete surgical resection of infected material while maintaining function. Despite recent advances, many patients with osteomyelitis fail aggressive medical and surgical therapy. More accurate diagnostic methods, better ways to assess and monitor the effectiveness of therapy, and novel approaches to eradicate sequestered bacteria are needed.