Treatment of osteomyelitis and musculoskeletal infections remains a problem today. There is no apparent end in sight as the incidence of trauma, especially in urbanizing Third World nations remains on the rise. Surgically invasive procedures, another source of infection, continues to increase as well. Treatment of chronic osteomyelitis has become a subspecialty within an orthopedic practice. It is best handled as a multidisciplinary approach and requires a knowledge of infectious disease and advanced soft tissue reconstruction procedures by the orthopedic surgeon managing such cases. It also requires that the surgeon understand the complex nature of biofilms so as to understand the complexities in eradication of these infections. This article gives an overview of these issues to help give the orthopedist a basic understanding to work as a framework to base treatment and care for patients with this disease state.