Mother's own milk (MOM) is known to decrease complications in preterm infants and when unavailable, it is recommended that preterm very low-birth weight infants be fed donor human milk (DHM). Due to the pasteurization, processing, and lactation stage of donors, DHM does not contain the same nutritional, immunologic, and microbial components as MOM. This review summarizes the differences between MOM and DHM, the potential effects on health outcomes, and the clinical implications of these differences. Finally, implications for research and clinical practice are discussed.