Antibiotic therapy and surgical drainage of the bone are the most commonly accepted forms of therapy for acute hematogenous osteomyelitis; the efficacy of these two treatment modalities, however, has not been fully established. Treatment regimens remain empiric and open to much controversy. Many contentious issues concerning the management of this disease have arisen because the natural history of the untreated condition has not been properly understood, because therapeutic regimens alternative to those empirically initiated and perpetuated have not been adequately tested, and because most follow-up studies have dealt with small numbers of patients over relatively short periods. A highly reproducible animal model of acute hematogenous osteomyelitis was developed and utilized in a reexamination of issues regarding the natural history and pathology of the disease and the influence of appropriate treatment.