We reviewed the available evidence regarding the effectiveness and safety of linezolid administration for the treatment of patients with orthopaedic infections due to multidrug-resistant Gram-positive cocci. Although the reports published to date include promising results for the use of linezolid for bone and joint infections, controlled studies will be needed to reach safe conclusions. Attention should be paid to adverse effects that may be related to linezolid administration, especially bone marrow suppression with prolonged administration of the antibiotic. In addition, early identification of linezolid-induced peripheral neuropathy is necessary because this may be an irreversible event.