The skin provides an effective barrier to the loss of body fluids and environmental assault. In addition to the physical barrier provided by the stratum corneum, the skin also contains a chemical barrier consisting of antimicrobial peptides (AMPs), which control microbial growth on the surface. These AMPs also have multiple roles as mediators of inflammation with effects on epithelial and inflammatory cells, influencing cell proliferation, wound healing, cytokine/chemokine production and chemotaxis. This review describes the range of peptides found in the skin, both constitutive and those induced in response to injury. The role these peptides play in normal skin function and in various skin conditions is described. A better understanding of their role in normal and skin disease may offer new strategies in skin disease, dermatology and as cosmeceuticals.