The concept and demonstration of genetic immunization (GI) was first introduced in 1992. At the time it appeared to be a revolutionary new approach in vaccinology. Since then, genetic immunization has been applied with much success in a wide variety of model and natural systems. It has also been used in several human clinical trials. Currently there is a general impression that genetic immunization has limitations inhibiting its broad use. The technique is thought to be poor at antibody production and more importantly not to work well in primates and humans (simian barrier). However, recent reports addressing these issues (poor antibody production and the simian barrier) showed improvements of GI to produce protective immune responses in humans. We propose that the apparent limitations of gene vaccines may arise from not using the technologies' potential to manipulate the immune system. This dearth of imaginative use is manifested in the tendency by some to term the technique DNA immunization. The apparent limitations of DNA vaccines may not be limitations for gene vaccines.