DNA vaccines, also referred to as genetic vaccines, are generating significant preclinical and clinical interest. It has been proven that the expression of an antigen or antigens from plasmid DNA (pDNA) may elicit both humoral and cellular immune responses. Therefore, DNA vaccines may have potential as new vaccines for important pathogens such as HIV, hepatitis C, tuberculosis, and malaria. However, the clinical results using "naked" pDNA have been disappointing in the breadth and depth of the immune response and the relatively high doses of pDNA needed to elicit a response. Clinical trials with the gene gun have been promising, but it is unclear whether this technology will be commercially viable. As a result, there exists a clear need for new vaccine delivery systems that can be administered at low doses to elicit strong humoral and cellular immune responses. One promising approach is the development of microparticles and nanoparticles as delivery systems for DNA vaccines. In this review, the application of microparticles and nanoparticles as DNA vaccine delivery systems will be critically reviewed with a primary focus on those systems that have generated in vivo immune responses.