Defensins are endogenous, small, cysteine-rich antimicrobial peptides that are produced by leukocytes and epithelial cells. Substantial evidence accumulated in recent years indicates that mammalian defensins are multifunctional and, by interacting with host cell receptor(s), participate in both the innate and adaptive antimicrobial immunity of the host. A better understanding of the function of defensins in immunity has implications for the development of potential clinical therapeutics for the treatment of infection or cancer. Here we will briefly outline the classification, genes, expression, and structure of mammalian defensins and focus on their roles in innate and adaptive immune response of the host.