The relatively low efficacy of DNA vaccines in inducing immune responses, especially in large animal species and humans, has impaired their practical use. Despite considerable effort expended on improving DNA vaccine delivery, only minute amounts of Ag are available for immune induction following DNA vaccination. Two complementary strategies have been used to improve and modulate the immune response induced by DNA vaccines: (i) supplementing DNA vaccines with plasmids encoding cytokines and (ii) targeting the Ag encoded by DNA vaccine through genetically fusing the Ag to molecules binding cell surface receptors. This paper reviews recent progress in these two areas and possible mechanisms responsible for the observed effects.