Care and outcomes for very preterm infants continue to improve, but important causes of mortality and acute and long-term morbidity associated with prolonged hospitalisation remain. Necrotising enterocolitis (NEC) and late-onset infection have emerged as the major causes of death beyond the early neonatal period and of neurodisability in very preterm infants. Although the pathogenesis of these conditions is incompletely understood, it appears to be related to the content and mode of delivery of the enteral diet, particularly the impact of immunonutrients from human breast milk on the microbial and metabolic balance within the immature intestine. Evidence exists to support investment in measures to help mothers to express breast milk as the primary source of nutrition for their very preterm infants. In the absence of maternal milk, pasteurised donor breast milk provides protection against NEC, but its nutritive adequacy is not clear and its cost-effectiveness is uncertain. Supplementation with individual immunonutrients, including immunoglobulins and lactoferrin, has not been shown to be effective in preventing NEC or infection in randomised controlled trials. The evidence base for prebiotics and probiotics is stronger, but concerns exist about the choice, safety and availability of formulations. Other strategies – including avoidance of drugs such as gastric acid suppressants that compromise innate immunity, as well as evidence-based progressive feeding strategies that reduce exposure to invasive interventions – are emerging as key components of care packages to reduce the burden of NEC, infection and associated growth and developmental faltering for very preterm infants.