Adult osteomyelitis remains difficult to treat, with considerable morbidity and costs to the health care system. Bacteria reach bone through the bloodstream, from a contiguous focus of infection, from penetrating trauma, or from operative intervention. Bone necrosis begins early, limiting the possibility of eradicating the pathogens, and leading to a chronic condition. Appropriate treatment includes culture-directed antibiotic therapy and operative debridement of all necrotic bone and soft tissue. Treatment often involves a combination of antibiotics. Operative treatment is often staged and includes debridement, dead space management, soft tissue coverage, restoration of blood supply, and stabilization. Clinicians and patients must share a clear understanding of the goals of treatment and the difficulties that may persist after the initial course of therapy or surgical intervention. Chronic pain and recurrence of infection still remain possible even when the acute symptoms of adult osteomyelitis have resolved.