In recent years, the prevalence of multiple drug-resistant strains of common Gram-positive pathogens has grown in many regions of the world. Increasingly, methicillin-resistant Staphylococcus aureus, coagulase-negative staphylococci, vancomycin-resistant enterococci, and penicillin-resistant pneumococci have been identified as causative organisms in serious and life-threatening infections. This increase in resistance highlights the need for new antimicrobial agents to expand the therapeutic armamentarium. Quinupristin/dalfopristin is the first of a unique class of antibiotics called streptogramins. It is characterized by a unique mechanism of action, intracellular activity, synergistic activity of its components, broad spectrum of activity against most Gram-positive cocci, common respiratory pathogens, and anaerobes, and demonstrated postantibiotic effect. Clinical evidence to date indicates that quinupristin/dalfopristin may be effective for the treatment of multidrug-resistant infections, especially those due to vancomycin-resistant enterococci and methicillin-resistant staphylococci. This article reviews the pharmacology, microbiology, and clinical experience with quinupristin/dalfopristin to date.