The ability of the cutaneous barrier to help defend the body against pathogens relies on both acquired and innate immune responses. Recently, a large body of research has suggested that a critical component of the innate immune response in the skin is 3 antimicrobial peptides: the cathelicidins, defensins, and dermcidins. These 3 classes of peptides have been shown to act as antimicrobials by directly inhibiting pathogen growth as well as potentiating other branches of the innate, humoral, and cell-mediated immune system. Here, we review the antimicrobial peptides with an emphasis on their role in the cutaneous immune response. We present an overview of defensin, cathelicidin, and dermcidin physiology, elucidating their various functions. In addition, we delve into the role of these peptides in specific dermatologic conditions including wound healing, atopy, and microbial infection. Finally, we discuss the future of antimicrobial peptide research including therapeutic options.