Topical DNA vaccines have been shown to elicit both broad humoral and cellular immune responses in vivo. The skin is an attractive site for the delivery of DNA antigens for DNA vaccination. However, due to skin’s barrier properties, the penetration of DNA and the applications of topical vaccination are limited. To improve permeability, chemical and physical approaches have been examined to decrease stratum corneum barrier properties. Topical vaccination has been achieved using topical application of naked DNA, DNA/liposomes or emulsion complex, liposomal cream, as well as physical methods such as stripping, electroporation, and micromechanical disruption methods. All methods resulted in a significant enhancement in humoral and cellular immune responses over naked DNA alone. To develop more cost-effective and needle-free vaccines, skin-targeted immunizations are required. This review focuses on the chemical and physical methods developed to enhance DNA delivery into skin.