Vaccination is historically one of the most important methods for preventing infectious diseases in humans and animals. Due to recent advances in understanding the biology of the immune system, a more rational design of vaccines and vaccination strategies such as those based on gene transfer has been proposed. In particular, naked DNA vaccination is emerging as a promising approach for introducing foreign antigens into the host, inducing protective immunity against infectious diseases and malignant tumours. Plasmid DNA vaccines offer several advantages in comparison to traditional vaccines such as safety, tolerability and feasibility in manufacture. Nevertheless, because of their poor immunogenicity, plasmid DNA vaccines need further implementation. Recent data suggest electroporation as a useful strategy to improve DNA-based vaccination protocols, being able to stimulate both the humoural and cellular immune responses. In preclinical trials, electroporation is successfully used in prime-boost combination protocols and its efficacy and tolerability have been demonstrated in Phase I clinical trials. Since these initial results appear promising, in the next future we will assist further developments of naked DNA vaccination associated to the electroporation technology. This approach not only provides the basis for human studies but also a practical application to veterinary medicine.