DNA vaccination is an attractive vaccination method. First, the production of plasmid DNA as a vaccine is considerably more cheap and simple than the production of recombinant protein. Second, the expression cassette of DNA vaccines can readily be modified, making DNA vaccines highly flexible. Finally, in animal models, DNA vaccination is able to induce potent cellular immune responses. Over the past decade, the focus in the DNA vaccination field has in large part moved from intramuscular immunization towards dermal administration. As a natural "porte d'entrée" for pathogens, the skin is rich in antigen-presenting cells, which are required for generating an efficient antigen-specific immune response. This chapter describes a DNA vaccination protocol that utilizes a simple tattooing device for the dermal delivery of plasmid DNA. This technique, called DNA tattooing, is capable of generating high frequencies of antigen-reactive T cells in mice and macaques.