In staphylococci, methylation of A2503 of 23S rRNA leads to resistance against several classes of antibiotics (oxazolidinones, phenicols, streptogramin compounds, lincosamidins and pleuromutilins). The corresponding resistance gene cfr is located on plasmid(s) and is transferable within and between staphylococcal species including Staphylococcus aureus. It first emerged in coagulase-negative staphylococci, later in Central Europe also in S. aureus ST9 and in methicillin-resistant S. aureus ST398, which have their main reservoir in pigs, and meanwhile also in nosocomial coagulase-negative staphylococci from Southern Europe and the USA, and furthermore in nosocomial methicillin-resistant S. aureus in Spain. Timely detection and targeted prevention of further dissemination in both human and veterinary medicine is warranted for preserving the activity linezolid as an important antibiotic for treatment of staphylococcal infections.