Human milk (HM) contains critical nutrients and possibly other neurotrophic factors that could benefit the less developed brain of preterm infants, particularly those with very low birth weight (VLBW). This study aims to systematically review the original studies to determine whether there is a reproducible independent effect of HM feeding on neurodevelopment outcome in preterm VLBW infants. Search of seven databases (PubMed, Cochrane, CINAHL, Embase, Proquest Research Library, Google Scholar, and Web of Science) identified 24 original studies. Each study was evaluated by two authors independently for 8 non-nutritive (study design, target population, a priori power calculation, adjustment for baseline growth status, postnatal complication, other confounders, observer blinding to feeding status, effect size) and 5 nutritive (definition and duration of HM intake, use of HM fortifier, source of HM data, infant formula used) methodology parameters, and consistency and directness of outcome measures. Thirteen reports of preterm infants with wide ranges of birth weights were excluded as none provided sufficient data to delineate the effects of HM feeding on developmental outcome of subjects with VLBW. Eleven reports included only VLBW children and 7 studies were reviewed after elimination of preliminary data from same cohort or lack of appropriate standardized testing or control group. These 7 studies (n = 18 to 704, median 219) were performed at <3 years (3 studies) and at 5 to 11 years (4 studies). Six studies were secondary analysis of data from other studies. Each study met or only partially met 4 to 10 methodological parameters. VLBW children with no neurological impairment fed HM achieved normal or low normal range of test scores. Formula feeding using older formulations was associated with a lower subtest score in 4 studies. There is no randomized clinical trial comparing the neurodevelopment outcome of HM versus formula or minimal HM feeding that included only children with VLBW. The role of HM in the neurodevelopment and cognitive function of VLBW children needs reassessment with high quality studies in the context of current formulations of HM fortifier and preterm formula.