Human milk (HM) is the ideal feeding for neonates, especially for premature infants. In particular, HM improves postnatal gastrointestinal maturation and functions; it improves infants’ immune function and host defences; and it improves long-term cognitive development.Unfortunately, HM also has some limitations when feeding premature infants. It does not provide sufficient amount of nutrients to cover their high requirements. Indeed, most premature infants developed several nutritional deficits and an extrauterine growth restriction when fed HM solely during neonatal hospitalization, especially very premature infants.HM fortifiers (HMFs) have been developed to compensate such postnatal undernutrition. They allow for providing additional minerals, protein and energy to premature infants. Most of them are available as powder that needs to be added to HM before feeding. The fortification of HM in premature infants has demonstrated that it significantly reduces osteopenia of prematurity and it also significantly improves postnatal growth. However, several studies still demonstrate the persistence of extrauterine growth restriction and some insufficient nutrient supply. Different reasons explain this phenomenon.Several recent reports have highlighted these new challenges and different options have been raised to improve these phenomena. The concept of individualized fortification has also been developed to compensate the variability in HM content before administration in premature infants.