Keywords: breastfeeding; human milk; human donor milk; promotion of breastfeeding; preterm infant; VLBW Human milk is recommended as the natural feeding for both term and preterm infants for the several health benefits associated with its consumption. The importance of human milk is not only limited to its nutritional value but it also includes the provision of bioactive factors involved in the optimization of infants' growth and neurodevelopment. A huge amount of researches indicates that the biological effects of human milk are dose dependent. Moreover, an increasing number of studies are showing that breast milk contains stem cells whose implications in infant neurodevelopment are under study. Hence, it is mandatory to promote initiation of breastfeeding as well as to support its duration [1][2][3][4].When taking into consideration feeding options for preterm infants, it should be highlighted that there is a biological hierarchy with milk of own mothers' being the first choice. When own mothers' milk is not available, donor human milk is recommended, whereas formula feeding should be the last choice [2].Human milk feeding represents a cost-effective strategy to reduce disease impact and associated costs in preterm infants, during the neonatal intensive care unit hospitalization [5]. Colaizy estimated that suboptimal feeding of extremely low birth weight infants would cost $27.1 million (CI $24 million, $30.4 million) in direct medical costs, $563,655 (CI $476,191, $599,069) in indirect nonmedical costs, and $1.5 billion (CI $1.3 billion, $1.6 billion) in cost attributable to premature death [6].The systematic review and meta-analysis published by Miller [7] summarized the available evidence in relation to the dose-dependent effect of human milk feeding on decreasing morbidity in infant born <28 weeks' gestation and/or birth weight <1500 g. Recent studies have assessed the different impact of human milk and preterm infant formula (PTF) feeding on one single outcome, thus limiting the in-depth analysis of the synergic protective co-effects led by the different nutritional and non-nutritional components of human milk against the most frequent comorbidities that affect premature infants. Remarkably, Miller considered the combination of five major morbidities (necrotizing enterocolitis, late onset sepsis, bronchopulmonary dysplasia, retinopathy of prematurity and neurodevelopment), pointing out the clear protective effect of human milk against necrotizing enterocolitis and possible reduction in late onset sepsis, severe retinopathy of prematurity and severe necrotizing enterocolitis. The comparison between various combinations of mixed feeding, human milk and preterm infant formula allowed for a specific investigation on the dose effect associated with human milk feeding.However, no conclusive evidence has been drawn on the incidence of bronchopulmonary dysplasia and on neurodevelopment, thus underlining the need for implementing research towards this direction.This systematic review allows for gaining further ins...