The incidence of infections caused by multidrug-resistant Gram-positive organisms is increasing despite advances in antibacterial therapy over the last 20 years. As the pathogens causing these infections are frequently resistant to most currently available antibacterials, they are extremely difficult to treat. Problematic pathogens include strains of Streptococcus pneumoniae resistant to beta-lactams and macrolides, viridans group streptococci resistant to beta-lactams and aminoglycosides, enterococci resistant to vancomycin and teicoplanin and highly resistant to penicillins and aminoglycosides, and Staphylococcus aureus resistant to methicillin, other beta-lactams, macrolides, lincosamides and aminoglycosides. Other important pathogens include Streptococcus pyogenes resistant to macrolides (and suspected to be resistant to penicillin), macrolide-resistant streptococci of groups B, C, and G, coagulase-negative staphylococci resistant to beta-lactams, aminoglycosides, macrolides, lincosamides and glycopeptides, multiresistant strains of Listeria and Corynebacterium and Gram-positive anaerobes, such as Peptostreptococcus and Clostridium, resistant to penicillins and macrolides. Thus, there is an urgent need for new antibacterial agents that are able to overcome multidrug-resistant mechanisms. The novel semisynthetic injectable streptogramin quinupristin/dalfopristin offers the prospect of effective treatment against many of the above pathogens.