DNA vaccination has been studied in the last 20 years for HIV vaccine research. Significant experience has been accumulated in vector design, antigen optimization, delivery approaches and the use of DNA immunization as part of a prime-boost HIV vaccination strategy. Key historical data and future outlook are presented. With better understanding on the potential of DNA immunization and recent progress in HIV vaccine research, it is anticipated that DNA immunization will play a more significant role in the future of HIV vaccine development.