Intravascular devices (IVDs) are widely used in modern day health care. Unfortunately, their use is associated with substantial risk of bloodstream infection (BSI) and sepsis, with increased hospitalization and hospital mortality. IVDs are the most common cause of nosocomial BSI. The wider use of new methodologies for diagnosis of IVD-related infection should allow earlier and more focused therapy and, especially, improve the accuracy of surveillance. Of all nosocomial infections, IVD-related BSIs are most amendable to prevention.