Linezolid is the only oxazolidinone antibiotic approved for clinical use. It inhibits bacterial protein synthesis by an original mechanism blocking the initiation phase, at a very early stage. It binds to the ribosome at the domain V of 23S rRNA and prevents transfer of amino acid on tRNA from A-site to P-site. Linezolid resistance was reported quickly after its marketing 10 years ago in clinical isolates of staphylococci and though it has progressed with the use of linezolid it remains rare (less than 1%). The three mechanisms of linezolid resistance described in staphylococci so far involve the 50S ribosomal subunit. This resistance is mainly associated with a variety of mutations in the genes encoding either 23S rRNA or exceptionally ribosomal proteins. The most common target site mutation observed clinically is the G2576 T. Recently, a new mechanism has been described by acquisition of the cfr gene. This gene, that methyls the adenine in position 2503 of domain V, is carried by plasmids that can promote the dissemination of linezolid resistance. Linezolid resistance could be detected by phenotypic methods according to usual standard procedures and confirmed by in-house genotypic methods. (C) 2012 Elsevier Masson SAS. All rights reserved.