Although intravascular catheters are indispensable for managing the care of critically ill patients, they can be associated with serious infection. Catheter-related bloodstream infections (CR-BSI) are a major cause of morbidity and mortality in the critical care setting. These infections are largely preventable. This article reviews the epidemiology and pathogenesis of these infections, the role of the critical care nurse in the diagnostic evaluation of CR-BSI, and strategies for their prevention.