The use of central venous catheters (CVC) is beneficial for the management of many groups of pediatric patients including low birth weight neonates, children with cancer, and those with chronic diseases that require frequent venous access such as cystic fibrosis and hemophilia. These CVCs are usually well-tolerated but infectious complications are relatively common and result in increased morbidity, hospitalization, and cost. Vascular access is often limited in pediatric patients. This affects both the diagnosis and management of catheter-related bloodstream infections (CR-BSIs) because obtaining a peripheral culture may not be possible and line removal may not be feasible. Despite limited data for specific interventions, new technologies for the prevention and treatment of CR-BSIs are effective in reducing CR-BSIs. Understanding of the pathogenic process and underlying risk factors of CR-BSIs is important in decreasing the life threatening complications and also improving the management strategies.