Antimicrobial peptides (AMPs) are cationic amphiphilic molecules with α-helix or β-sheet linear motifs and linear or cyclic configurations. For their role in ‘defense and offense’, they are present in all living organisms. AMPs are named so, as they inhibit a wide array of microbes by membrane pore formation and subsequent perturbation of mitochondrial membrane ionic balance. However, their functional repertoire is expanding with validated roles in cytotoxicity, wound healing, angiogenesis, apoptosis, and chemotaxis [1]. A number of endogenous AMPs have been characterized in human body such as defensins, cathelicidins, histatins etc. They mediate critical functions, but when homeostasis is broken, they turn hostile and initiate inflammatory diseases. This review discusses the sources of therapeutic AMPs; auto-immunity risks of endogenous AMPs, and their dermatological applications; normally overlooked risks of the peptides; and scopes ahead. This holistic work is expected to be a valuable reference for further research in this field.