Of the approximately 3.9 million births annually in the United States, more than 61,000 occur at gestational ages below 32 weeks and are thus at the highest risk for the development of necrotizing enterocolitis (NEC). In addition to its substantial direct burden of illness to babies and families in both the short and long term, the condition has important economic implications. In this chapter, we explore not only the increased costs of caring for infants who develop NEC but also the costs of prevention and the potential benefits of optimizing the health care delivery system to ensure that therapies are delivered most efficiently.