Controversy surrounds the role of central venous catheters (CVCs) impregnated with antimicrobial agents in the prevention of catheter-related bloodstream infection (CRBSI). We reviewed the current literature to evaluate the efficacy of antimicrobial-impregnated CVCs for preventing CRBSI. Eleven randomized studies published in article form were identified that included a control group that received nonimpregnated CVCs. We evaluated study methodologies, inclusion of key patient characteristics, use of clinically relevant end points, and molecular-relatedness studies. Review of these 11 trials revealed several methodological flaws, including inconsistent definitions of CRBSI, failure to account for confounding variables, suboptimal statistical and epidemiological methods, and rare use of clinically relevant end points. This review also failed to demonstrate any significant clinical benefit associated with the use of antimicrobial-impregnated CVCs for the purpose of reducing CRBSI or improving patient outcomes. More rigorous studies are required to support or refute the hypothesis that antimicrobial-impregnated CVCs reduce the rate of or prevent CRBSI.