Oxazolidinediones represent a class of antibacterials of which linezolid is the one available agent. Linezolid is primarily active against aerobic gram-positive pathogens, including penicillin-resistant pneumococci, methicillin-resistant staphylococci and enterococci (both E faecalis and vancomycin-sensitive and vancomycin-resistant E faecium). Linezolid is bacteriostatic against all of these pathogens. Linezolid-resistant and vancomycin-resistant enterococci and linezolid-resistant S aureus and S epidermidis have been observed, however. The oral bioavailability of linezolid is complete, with serum levels approaching those observed with intravenous administration. The drug is eliminated primarily by nonrenal mechanisms. The primary toxicity is bone marrow suppression with long-term therapy, particularly the platelet and white blood cell lines. Other adverse effects include neuropathy and mitochondrial toxicity with long-term use. Linezolid is a mild monoamine oxidase inhibitor and while concomitant use of selective serotonin reuptake inhibitors may result in a serotonin syndrome, most patients can safely receive both agents together. In the treatment of methicillin-resistant S aureus pneumonia, linezolid is superior to vancomycin. While linezolid is modestly superior to vancomycin in confirmed methicillin-resistant S aureus pneumonia, it offers little in the empiric treatment of hospital acquired– or ventilator-associated pneumonia. Of particular concern are the increasing reports of linezolid-resistant Enterococcus and staphylococci, which reinforce that this agent should be used judiciously.