The development of infant formula with optimized protein quality and quantity has been, and still is, the subject of intense investigation. A better understanding of the protein composition of breast milk and infant needs in association with technological breakthroughs in cow's milk fractionation, has led to the development of infant formulas with a protein content that is closer to that of human milk. Today, infant formulas with a protein/energy ratio of 1.8 g/100 kcal are commercially available. These formulas have been shown to be safe and nutritionally adequate for term infants. However, the short-term and potentially long-term metabolic benefits of formulas with reduced protein content have still to be elucidated and are currently under investigation. In addition to providing amino acids as building blocks for growth, milk is the source of numerous bioactive factors/hormones which are involved in multiple physiological processes. Continuous efforts are being made to identify new bioactive compounds in human milk. However, a better understanding of their biological functions in suckling infants as well as a comparison with their bovine counterparts are needed. Technological processes, which preserve some bioactive factors in cow's milk already exist. These processes could be applied to infant formulas.