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DNA immunization is an attractive technology owing to its potential to induce balanced and long-lived immune responses. However, progress into the clinic has been hampered by the relatively low magnitude of the immune response typically induced following administration in large target species, which is likely due to low transfection efficiency as well as insufficient recruitment of antigen-presenting cells to the injection site. Electroporation addresses both of these limitations by inducing transiently enhanced cell membrane permeability, thus facilitating uptake of the DNA into the host cell and creating a low level of inflammation conducive to enhanced influx of antigen-presenting cells to the injection site. Consequently, electroporation-mediated delivery of DNA vaccines results in very significant improvements in the transfection efficiency and immune responses in comparison to conventional injection. Importantly, electroporation is effective in virtually every animal model tested to date and has a favorable safety profile, which is promising for clinical application. In support of the potential for electroporation in human disease situations, early clinical results suggest that the immunogenicity of DNA vaccines is greatly improved when delivered with electroporation.