Lactoferrin is a highly conserved protein from an evolutionary perspective, with a wide range of roles related to protection from infection and promotion of nutritional status. Infection, malnutrition and intestinal pathologies are key inter-related problems, represent important threats to survival and are associated with adverse long-term health outcomes after preterm birth. Lactoferrin is available as a commercial extract from bovine milk and offers potential as a therapeutic intervention for preterm infants modulating infections and intestinal pathologies. In this review we explore the structure, direct antimicrobial effects, modification of host immune function and gastrointestinal effects of lactoferrin. Current trial data are reviewed, and research priorities and challenges identified and discussed.