Despite use that spans more than four decades, vancomycin remains one of the most important antibiotics in orthopaedic practice. It has increased in importance in the last decade because of the growing resistance of many gram-positive bacteria to β-lactam antibiotics, such as penicillins and cephalosporins. These gram-positive bacteria, especially Staphylococcus aureus and coagulasenegative staphylococci, cause a large proportion of the infections encountered in orthopaedic surgical practice, especially those involving implanted hardware.