Epidemiological studies conducted over the past thirty years to investigate the protective function of human milk strongly support the notion that breastfeeding prevents infantile infections, particularly those affecting the gastrointestinal and respiratory tracts. However, more recent clinical and experimental observations have been directed to the notion that human milk not only provides passive protection, but also can directly modulate the immunological development of the recipient infant. For example, breastfed infants have a reduced incidence of allergic diseases and other pathological conditions associated with an auto- or dysregulated immunity, such as Crohn's disease and ulcerative colitis,insulin-dependent diabetes mellitus and some lymphomas, long after the termination of breastfeeding. The study of this remarkable defence system in human milk has been difficult due to its biochemical complexity, the small concentration of certain bioactive components, the lack of specific reagents to quantify these agents, the compartmentalization of some of these agents and the dynamic quantitative and qualitative changes of milk during lactation. Nevertheless, a host of bioactive substances including hormones, growth factors and immunological factors such as cytokines have been identified in human milk. Some of these factors are abundant in the early milk while the neonatal immune system is immature, suggesting that they may «compensate» for such developmental delays. Functional interactions among bioactive factors present in human milk as well as common features, such as their physical state in milk, are also only recently being discovered. Furthermore, there is still a substantial lack of knowledge about the origin of many of these factors present in human milk and precisely how they affect the recipient infant. Some of the findings related to the presence, protective function and immunomodulating activity of milk-borne substances are presented.