Relatively high amounts of protein are required to achieve normal fractional protein synthetic rates during the late second through early third trimester of fetal growth. Once preterm infants achieve higher protein intakes for sustained periods, growth begins to approximate that of the normally growing fetus and long-term neurodevelopmental outcomes are improved. Preterm formulas have been developed that are enriched in protein. This review discusses several factors when using standard preterm formulas and high-protein preterm formulas in the neonatal intensive care unit, with an emphasis on quantity and quality of enteral protein delivery and risks to insufficient and/or excess protein administration.