The concept of DNA immunization was first advanced in the early 1990s, but was not developed because of an initial lack of efficiency. Recent technical advances in plasmid design and gene delivery techniques have allowed renewed interest in the idea. Particularly, a better understanding of genetic immunization has led to construction of optimized plasmids and the use of efficient molecular adjuvants. The field also took great advantage of new delivery techniques such as electrotransfer. This is a simple physical technique consisting of injecting plasmid DNA into a target tissue and applying an electric field, allowing up to a thousandfold more expression of the transgene than naked DNA. DNA immunization mediated by electrotransfer is now effective in a variety of preclinical models against infectious or acquired diseases such as cancer or autoimmune diseases, and is making its way through the clinics in several ongoing phase I human clinical trials. This review will briefly describe genetic immunization mediated by electrotransfer and the main fields of application.