Intravascular devices (IVDs) are widely used for vascular access but are associated with substantial risk of development of IVD-related bloodstream infection (BSI). The development of novel technologies, which are based on an understanding of pathogenesis, promises a quantum reduction in IVD-related infections in an era of growing nursing shortages. Infections of short-term IVDs (that is, those in place <10 days), including peripheral venous catheters, noncuffed and nontunneled central venous catheters (CVCs), and arterial catheters, derive mainly from microorganisms colonizing the skin around the insertion site, which most often gain access extraluminally. More-effective cutaneous antiseptics, such as chlorhexidine, a chlorhexidine-impregnated sponge dressing, CVCs with an anti-infective coating, anti-infective CVC hubs, and novel needleless connectors, have all been shown to reduce the risk of IVD-related BSI in prospective randomized trials. The challenge for the future will be to identify new preventative technologies and to begin to adapt more widely those technologies already shown to be efficacious and cost-effective.