Introduction: Central Line-Associated Bloodstream Infections (CLABSIs) are a major cause of increased mortality, morbidity and healthcare costs in neonatal intensive care units (NICUs) patients. Despite CDC's efforts to reduce infection rates, patients often suffer consequences. The objective of this study is to perform a systematic review of strategies utilized in the neonatal population and evaluate them with the current CDC's guidelines to assess the effectiveness of bundles in preventing CLABSI in NICUs. Methods: A systematic literature search was conducted using CINAHL Plus with Text, Cochrane Database of Systematic Reviews and MEDLINE from January 2008 up to 2018. There were multiple search terms used and these included "neonate OR newborn OR infant", "CLABSI OR central line-associated bloodstream infection", "intervention OR prevention" and "bundle". The search solely focused on the outcome of infant patients. Therefore studies were excluded for the following criteria: being non-peer reviewed, being published before 2008, and being a case in which CLABSI was assessed in patients outside the NICU. See Table 4 and 5 for further information. Results: Eight articles were eligible for inclusion all of which CDC's guidelines were implemented in their strategy of intervention. The systematic review showed that adherence to care bundles decreases infection rates drastically. All eight articles reported a significant decrease in CLABSI rates following the implementation of the bundle set by CDC with two studies achieving a CLABSI rate of zero. Author's Conclusion: Implementation of care bundles showed a success in reducing CLABSI rates in the NICUs; however none of the studies endorsed a specific bundle application utilized to achieve its intended goal. Some practices adopted CDC's guidelines more than others and those showed a greater decrease in infection rate. In addition, it is evident that nurses deliver the best care when preventing an infection. Further research is needed to assess the effectiveness of a specific bundle element.