Central venous catheters (CVCs) are regularly used in intensive care units, and catheter-related bloodstream infection (CRBSI) remains a leading cause of healthcare-associated infections, particularly in preterm infants. Increased survival rate of extremely-low-birth-weight infants can be partly attributed to routine practice of CVC placement. The most common types of CVCs used in neonatal intensive care units (NICUs) include umbilical venous catheters, peripherally inserted central catheters, and tunneled catheters. CRBSI is defined as a laboratory-confirmed bloodstream infection (BSI) with either a positive catheter tip culture or a positive blood culture drawn from the CVC. BSIs most frequently result from pathogens such as gram-positive cocci, coagulase-negative staphylococci, and sometimes gram-negative organisms. CRBSIs are usually associated with several risk factors, including prolonged catheter placement, femoral access, low birth weight, and young gestational age. Most NICUs have a strategy for catheter insertion and maintenance designed to decrease CRBSIs. Specific interventions slightly differ between NICUs, particularly with regard to the types of disinfectants used for hand hygiene and appropriate skin care for the infant. In conclusion, infection rates can be reduced by the application of strict protocols for the placement and maintenance of CVCs and the education of NICU physicians and nurses.