Antimicrobial peptides represent an important aspect of the innate defense system that contributes to the control of bacterial colonization and infection. As studies have progressed it has become clear that antimicrobial peptides manifest other functions in addition to their antimicrobial effects. These functions include chemotaxis of numerous types of host cells involved in both the innate and adaptive immune responses. In this review, the antimicrobial activity, the regulation and the contribution to host homeostasis of alpha-defensins and LL-37, as well as of beta-defensins, are discussed in the context of their specific tissue locations in the junctional epithelium and oral epithelium, respectively.