While mortality associated withrespiratory distress syndrome in premature infants hasbeen reduced, other morbidities associated with pretermbirth, including necrotizing enterocolitis (NEC) and sepsis,are becoming more relevant. Although the pathogenesisof these diseases remains incompletely defined andunderstood, one of the leading risk factors is the immaturityof the immune system, which determines the tendencyof premature infants to develop excessive inflammatoryresponse and disruption of the formation of "healthy" gutmicrobiota. Breastfeeding provides a protective effect dueto the wide range of immunologically active components ofthis unique product. Current data suggest that donor milk isthe best alternative to native breast milk, as the use of theformula is primarily associated with an increased risk ofNEC. The use of individual immunological components ofbreast milk, such as lactoferrin or immunoglobulins, doesnot reduce the incidence of this disease. At the same time,lactoferrin may reduce the incidence of late-onset sepsis.Pro- and prebiotics have better evidence for the preventionof these diseases, however, questions remain about thechoice of the most effective strains, dosage, duration,and safety of their use, especially in extremely prematureinfants with a birth weight <1000 g. Combined data fromexperimental and clinical studies indicate that human milkoligosaccharides may protect against NEC, however, morereliable evidence of their effectiveness is needed, as wellas the solution of technological problems associated withthe synthesis of individual oligosaccharides and their useas individual supplements. For today, clinical practices toensure mothers are optimally supported to express theirown breast milk in order to optimize breastfeeding, earlyenteral feeding, and faster increase in daily feeds are keynutritional methods to prevent NEC and late infections inpreterm infants.