Various methods have been reported and used clinically to augment the nutrient supply for human milk-fed premature infants. These methods include specialized maltinutrient powdered mixtures (fortifiers), complete liquid formulas designed to be mixed with human milk, complete powdered formulas to be mixed with human milk, and alternate feeding of human milk and preterm formula. Although the optimum nutrition of premature infants is unknown, data are accumulating to suggest that human milk, fortified with additional nutrients, is appropriate for tube-fed infants. The use of fortified human milk typically provides premature infants adequate growth, nutrient retention, and biochemical indices of nutritional status when fed at approximately 180 mL/kg/d compared with unfortified human milk. Data are needed to determine the precise quantity of nutrients to be added as supplements. Nutrient interactions have not been explored in detail. Although large quantities of calcium seem to be needed, the exogenous calcium may affect fat absorption adversely. Manipulation of milk may affect the intrinsic host-defense properties of the milk. Compared with preterm formula, the feeding of fortified human milk may provide significant protection from infection and NEC. Lastly, the potential stimulation of an enteromammary pathway through skin-to-skin contact provides species-specific antimicrobial protection for premature infants. Several of these areas require additional exploration. Thus, for premature infants, neonatal centers should encourage the feeding of fortified human milk, together with skin-to-skin contact, as reasonable methods to enhance milk production while potentially facilitating the development of an enteromammary response.