The etiologic importance of anaerobic microorganisms in bone and joint infections in certain settings has recently been emphasized. These settings include recovery of Actinomyces species, hematogenously acquired infection, the presence of anaerobes in pure culture, and prosthetic-joint infection. Frequently, mixed aerobic-anaerobic bone or joint infection develops as a consequence of infection in adjacent areas. The incidence with which anaerobes are present in these settings is undoubtedly underestimated and may often be unappreciated in regard to the selection of therapeutic agents. Therefore, a practical approach to the treatment of infections involving anaerobes that is based on our current knowledge is necessary. Animal models are now available for study of anaerobic osteomyelitis. In conjunction with prospective human studies utilizing careful microbiologic techniques, it should be possible to determine the significance of anaerobic bacteria when a polymicrobial flora is present in bone and joint infections.