Gram-positive organisms, particularly staphylococci and streptococci, are responsible for the majority of bone and joint infections. The rising incidence of antimicrobial resistance among Staphylococcus aureus, coagulase-negative staphylococci and enterococci means that novel antibiotics with unique mechanisms of antimicrobial activity are needed, especially in orthopedic infections. Linezolid is the first of the oxazolidinones, a new class of antibacterial agents particularly effective against Gram-positive infections including methicillin- and vancomycin-resistant strains. With an excellent oral bioavailability and acceptable safety profile, linezolid offers a valuable alternative to more traditional therapies, such as glycopeptides. No large randomized trials have been published on its use in patients with orthopedic infections, but early results are encouraging. Reported adverse events, especially bone marrow suppression and optic neuropathy seen with prolonged administration, mean that treatment of such patients must be undertaken with careful follow-up of laboratory tests. Until now, little resistance has been reported.