Gene gun-mediated, intracellular delivery of small quantities of antigen expression vectors within the epidermis results in transient antigen expression and the induction of humoral, cellular and protective immune responses in a variety of animal models. The effectiveness of this vaccine technology in both rodents and larger animals is consistent with its reliance upon a physical, intracellular delivery process with minimal interspecies variation. This article reviews the development of gene gun instrumentation and summarizes progress in inducing and characterizing immune responses elicited via the intracellular delivery of DNA-coated gold particles to the epidermis.