To improve the efficacy of DNA immunization epidermal Langerhans cells are attractive targets to deliver antigen-encoding plasmid DNA. Topical vaccination with naked plasmid DNA has been shown to induce immune responses, and their potency might be improved by chemical and physical methods aimed to enhance the efficiency of plasmid DNA delivery into the skin. Cytokines have also been evaluated as adjuvants for DNA vaccines because they influence the host immune response. This review focuses on the action of several cytokines tested as molecular adjuvants for DNA vaccines and the combination of them with the DermaVir Patch vaccine. DermaVir vaccine, topically administered under a patch, consists of a plasmid DNA that is chemically formulated into a nanoparticle to support vaccine delivery into epidermal Langerhans cells and to induce antigen-specific memory T cells.