As an attractive alternative to conventional vaccines, DNA vaccines play a critical role in inducing protection against several infectious diseases. In this review, we discuss the advantages that DNA vaccines offer in comparison to conventional protein-based vaccines. We discuss strategies to improve the potency and efficacy of DNA vaccines. Specifically, we focus on the potential use of DNA-based vaccines to elicit broad-spectrum humoral and cellular immunity against influenza virus. Finally, we discuss the advances made in the use of DNA vaccines to prevent avian H5N1 influenza.