Cationic host defence peptides are an evolutionarily conserved component of the immune system and have been found across a wide variety of species. In lower organisms they comprise a major component of the defensive repertoire, whereas in higher species they are a part of the complex immune system dedicated to protecting against infection. Human neutrophils contain large amounts of the cationic alpha-defensin peptides, HNP-1-3, as well as HNP-4, which is present in lower amounts, while two Paneth cell alpha-defensins, HD-5 and HD-6, are also found in the gut. It is now becoming clear that alpha-defensins have multiple functions in the immune system; however, it is also apparent that although there is redundancy in their function, they also each have unique roles within the ever-increasing complexity of the immune system.