Central line-associated bloodstream infection (CLABSI) occurs when microorganisms colonize the central venous catheter and enter the bloodstream, causing bacteremia or sepsis. Four pathways of contamination exist: extraluminal migration of skin organisms along the external catheter surface from the insertion site (most common in short-term catheters, usually within 10 days); intraluminal contamination through the catheter hub from manipulation without proper aseptic technique (most common after 10 days); hematogenous seeding from a distant infection site to the catheter tip biofilm; and rarely, contaminated infusate. Staphylococcus epidermidis and Staphylococcus aureus are the most common causative organisms, followed by Enterococcus, Candida, and gram-negative bacilli. Once bacteria adhere to the catheter surface, they produce a glycocalyx biofilm matrix that protects them from antibiotics and host immune defenses, making catheter removal often necessary for cure. CLABSI mortality rates are 12-25%, with each infection adding $46,000 in healthcare costs and 7-10 days of additional hospitalization.