The predominant source of intravascular catheter-related bloodstream infections has been a research and clinical question for more than 30 years. During that time, we've moved from the position of a single source predominating in all clinical scenarios to a more realistic appraisal that both skin at the insertion site and the catheter hub/connector (ie, an extraluminal and an intraluminal source of infection, respectively) are important and that maximally effective prevention programs must address both sources of infection.