Innate antimicrobial peptides are considered to play an important role in host defense against microbial invasion. They are expressed in a wide variety of organisms. In the case of human beings, defensins and the cathelicidin LL-37 appear to be the major microbicidal peptides. With respect to human neonates, only few investigations have been performed in this context, revealing the presence of α-defensins and LL-37 in neutrophils and vernix caseosa. In addition, β-defensins are present in tracheal aspirates and breast milk, whereas LL-37 has been detected in the skin of the newborn baby. During recent years, immunomodulatory activities such as chemotaxis have emerged as important functions of antimicrobial peptides. Thus, these innate effectors may work synergistically to provide a first line of defense against infection, as well as to promote interactions between the innate and adaptive immunity in newborn infants.