Human neonates are born with an immature and naive acquired immune system, and many of the innate components of mucosal immunity are not fully developed. Thus, the innate immune system of human milk is an important complement to the mucosal barrier of the developing gut. The nursing mother provides her infant many protective agents through milk, a growing number of which have been identified as isolates of milk in laboratory models of infection. The number, the potency, and the importance of these protective agents are probably greater than previously thought. For example, many potent protective agents are not found in milk until digestion releases antimicrobial agents such as fatty acids and peptides. An alternate conformer of alpha-lactalbumin forms from milk in the stomach and inhibits cancer cells. Many of the protective constituents of human milk inhibit different aspects of a pathogenic process, creating a synergy, where much lower concentrations of each component become protective. Some components have a temporal and a spatial specificity that would cause their protective role to go unrecognized by most laboratory models of infection. Some protective components had remained underappreciated because of technical challenges in their isolation and testing. Recent reports suggest that human milk contains a highly potent mixture of protective agents that constitute an innate immune system, whereby the mother protects her infant from enteric and other diseases. These human-milk components may represent a rich source of novel classes of therapeutic agents against human pathogens.