Central venous catheter infections are the leading cause of healthcare-associated bloodstream infections and contribute significantly to mortality and morbidity in neonatal intensive care units. Moreover, infection poses significant economic consequence which increased hospital costs and increased length of hospital stay. Prevention strategies are detailed in guidelines published by the Centers for Disease Control and Prevention (CDC) in the United States; nevertheless, recent surveys in neonatal units in the United States, and Australia and New Zealand demonstrate these are not always followed. This review discusses the numerous evidence-based strategies to prevent catheter infections including hand hygiene, maximal sterile barriers during insertion, skin disinfection, selection of insertion site, dressings, aseptic non-touch technique, disinfection of catheter hubs/ports, administration set management, prompt removal of catheter, antibiotic locks, systemic antibiotic prophylaxis and chlorhexidine bathing. Furthermore, it will describe different strategies that can be implemented into clinical practice to reduce infection rates. These include the use of care bundles including checklists, education and the use of CVC teams.