Cathelicidins are a ubiquitous family of host defence peptides (HDPs) in vertebrate animals. Unlike other HDP families, they are defined by the common and relatively well conserved proregion rather than the mature active peptides, which are highly diverse and conform to at least five different structural groups. They seem to have fol-lowed a rather distinctive evolutionary path in their development. Cathelicidin-derived peptides play a relevant role in defending the host against microbial infection, by displaying both a broad-spectrum, direct antimicrobial activity and the capacity to modulate other host responses to infection and injury. Both types of effect depend on the structural type, which in turn affects the particular mode of action of each peptide. This chapter begins by briefly describing the discovery of cathelicidins before dis-cussing their molecular diversity and con-sidering their evolution. It then considers their expression and processing, the struc-ture-dependence of the distinct modes of action shown by different members, and briefly touches on the
