Bone and joint infections are a cause of rising concern, mainly owing to the increasing number of traumatic accidents, the appearance of new groups of patients at risk, the widespread use of prosthetic devices and the emergence of new patterns of antimicrobial resistance. Treatment guidelines and particular strategies for the management of such infections are reviewed. Decisions regarding the best therapeutic modality can be challenging and take into account the factors involved in infection staging, along with a better knowledge of the bacterial biofilm status. Surgery and antibiotic therapy are the keystones of the management, but overall the timing and length of treatment and follow-up should be posed to obtain the best quality of life for the patient. These infections are characteristically intriguing and sometimes need multiple surgical interventions and several courses of therapy. A multi-disciplinary approach is worthwhile in each institution. The collaboration of a specialized team composed by surgeons, pathologists, microbiologists and clinicians will permit diagnostic and therapeutic protocol-guided decisions.