Within the last decade, several peptides have been discovered on the basis of their ability to inhibit the growth of potential microbial pathogens. These so-called antimicrobial peptides participate in the innate immune response by providing a rapid first-line defense against infection. Recent advances in this field have shown that peptides belonging to the cathelicidin and defensin gene families are of particular importance to the mammalian immune defense system. This review discusses the biology of these molecules, with emphasis on their structure, processing, expression and function. Current evidence has shown that both cathelicidins and defensins are multifunctional and that they act both as natural antibiotics and as signaling molecules that activate host cell processes involved in immune defense and repair. The abnormal expression of these peptides has also been associated with human disease. Current and future studies are likely to implicate the presence of antimicrobial peptides in several unexplained human inflammatory disorders and to provide novel therapeutic approaches to the treatment of disease.