Clinicians use clinical symptom, blood culture, and central venous catheter (CVC) culture data to detect CVC-related sepsis. The lack of clear and consistent definitions for what constitutes accurate clinical symptom assessments, coupled with the different combinations for blood and CVC culture results, contribute to clinicians' uncertainty about the presence of CVC-related sepsis. When clinical symptoms do not correlate with laboratory culture results, patients are exposed to risks associated with CVC manipulation and inappropriate antibiotic therapy. Clinicians must recognize the sources of uncertainty when assessing patients for CVC-related sepsis.