Central venous catheters have become essential devices for the management of critically and chronically ill patients; however, their use is often complicated by catheter-related bloodstream infections (CRBSIs), many of which could be prevented. This report is based on a literature review of more than 100 published articles in intravascular catheter-related infections. This review focuses on the most recent advances in the methods of diagnosis of CRBSI as they relate to its pathogenesis and on novel preventive techniques and approaches to management. Catheter-related bloodstream infections may be diagnosed by different methods, including simultaneous quantitative blood cultures, with the central blood culture yielding at least 5-fold colony-forming units greater than the peripheral blood culture, and simultaneous blood cultures, whereby the catheter-drawn blood culture becomes positive at least 2 hours before the peripheral blood culture. Novel preventive techniques include the use of ionic silver, an anticoagulant/antimicrobial flush solution, a new aseptic hub, and antimicrobial impregnation of catheters and dressings. Management of CRBSIs should be based on whether the infection is complicated or uncomplicated. Novel technologies that have been proved to aid in the diagnosis and prevention of CRBSIs should be considered in clinical practice. The management approach should be based on the type of microorganism causing the infection and on whether the infection is complicated or uncomplicated.