Coagulase-negative staphylococcal bacteremia and infections of prosthetic medical devices have become major clinical problems. Efforts to differentiate contaminating from infecting isolates consume the time of microbiology laboratory personnel; decisions over when and with what to institute therapy for multiresistant isolates consume the energy of clinicians; and the need to institute expensive parenteral antimicrobial therapy consumes the hospital pharmacy budget. It is clear that the increased incidence of coagulase-negative staphylococcal infections is the result of medical progress and is due to the use of invasive and indwelling medical devices. Multiresistant organisms have evolved that will survive in the presence of antimicrobial agents designed to eradicate more traditional pathogens. They have an ecological niche on human skin from which they are difficult to eradicate, and they have adapted themselves to survive on inert devices designed to persist indefinitely in the human body. Since it is likely that the use of prosthetic medical devices will continue to increase, we need to device innovative strategies for the diagnosis, treatment, and prevention of infections of these indwelling foreign bodies. Studies that will address these issues should be a major goal of future research on hospital-acquired infections.