Intravascular devices (IVDs) are widely used for vascular access but are associated with a substantial risk of IVD-related bloodstream infection (BSI). The development of novel technologies based on our understanding of pathogenesis promises a quantum reduction in IVD-related infections in an era of growing nursing shortage. Infections of long-term IVDs (most are in place for > or =10 days), including cuffed and tunneled central venous catheters (CVCs), implanted subcutaneous central venous ports, and peripherally inserted central catheters (PICCs), are primarily due to microorganisms that gain access to the catheter hub and lumen. Novel securement devices and antibiotic lock solutions have 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 more-widely adapt those technologies that have already been shown to be efficacious and cost effective.