Mother's own human milk is the best nutrition for infants, especially preterm very-low-birth-weight (VLBW) (≤1,500 g) infants, because of its immune-modulatory constituents that strengthen the infant's host defense, provide protection against infections, and decrease the risk of necrotizing enterocolitis (NEC). When mother's own milk is unavailable or insufficient, donor human milk is considered the best alternative, especially for preterm VLBW infants. However, to assure biological safety, donor milk must be pasteurized. This results in partial or complete inactivation of some of the immunomodulatory constituents of human milk, which confer host defense. This review summarizes the current evidence regarding the effects of pasteurization on the different immunological constituents of donor milk, and their clinical significance, especially in relation to prevention of NEC.