Vancomycin is a narrow-spectrum bactericidal antistaphylococcal antibiotic that was introduced in 1956 because of its efficacy against resistant penicillinase-producing staphylococci. It was effective for serious staphylococcal infections for which no satisfactory alternative to penicillin G was available at the time. When methicillin and the other semisynthetic penicillins and the cephalosporins were introduced, the role of vancomycin was relegated to the alternative therapy of choice when the penicillins and the cephalosporins could not be used. In the future, vancomycin may be used more frequently in (1) methicillin-resistant Staphylococcus aureus infections, (2) streptococcal endocarditis in conjunction with an aminoglycoside in patients intolerant to penicillin or ampicillin, (3) infections associated with prosthetic devices caused by organisms with multiple antibiotic resistance, and (4) antibiotic-induced enterocolitis associated with Clostridium difficile.