Background: Development of necrotizing enterocolitis is multifactorial, with contributing factors that are unique to the preterm infant in the neonatal intensive care unit (NICU). The use of probiotics may reduce these risk factors. Purpose: To evaluate evidence of biologic plausibility for probiotic supplementation to mitigate key risk factors implicated in the development of disease and show recent evidence of safety and effectiveness. Data Sources: A literature survey of electronic databases, including PubMed, Cochrane Database of Systematic Reviews, and CINAHL, was conducted. Study Selection: Selection terms included "necrotizing enterocolitis, " "probiotics, " and "prematurity. " Reviews that were included were full text, in English, and published in the last 5 years. Ten systematic reviews of randomized controlled trials were extracted from 749 records. Excluded were studies that used adjuncts to probiotics, such as lactoferrin or prebiotics, and studies of probiotics given antenatally. Data Extraction: Two independent reviewers extracted data to AMSTAR 2, a critical appraisal tool for systematic reviews of randomized or nonrandomized studies of healthcare interventions. Results: All the reviews found statistically significant reductions in necrotizing enterocolitis rates after supplementation with probiotics. None of the reviews reported adverse effects. Implication for Practice and Research: Probiotic supplementation with specific strains reduces risk for necrotizing enterocolitis. To advance probiotic use in the NICU, additional high-quality trials are needed to focus on specific strains or combinations of strains and to evaluate dosing and duration of treatment.