Antimicrobial peptides (AMPs), also known as host defense peptides, are ubiquitous naturally occurring molecules secreted by various cell types of the body. In the skin, AMPs serve as a first-line innate immune defense against exogenous microorganisms, and they orchestrate adaptive immune responses to exert several immunomodulatory functions. Emerging evidence indicates that AMPs not only contribute to certain inflammatory skin diseases but also play a role in skin tumor carcinogenesis. Available data support the hypothesis that AMPs possess both pro-tumor and anti-neoplastic properties. Although inconsistent observations reported by multiple studies make it challenging to summarize the precise roles of AMPs in cancer, the differential expression of AMPs in skin cancers, such as the increased expression of human beta-defensins in squamous cell carcinoma and the ability of cathelicidin LL-37 to induce malignant melanoma cell invasion, implies they have procancer activities. On the other hand, the observation that certain AMPs show cytotoxic activity against cancer cells of the colon and kidney suggests their inherent antitumor properties. In this review, we describe the roles and mechanisms of AMPs in skin cancer development. We believe that further research is needed to elucidate the impact of these AMPs in skin cancer biology and to explore their potential roles as diagnostic/prognostic biomarkers and as novel therapeutic targets.