Over the past 15 years, advances in molecular biology have permitted in vitro and in vivo gene transfer into mammalian cells. Genetically engineered microorganisms are highly promising developments for gene therapy and the future of vaccines. Such vectors constitute genuine tools for high level expression of heterologous genes for both therapeutic and induced immunity applications. Several vector systems have emerged with different relative advantages and limits depending on the proposed application. Adenovirus (Ad) has gained our interest, and in this review we focus on its applicability as a vaccine vector. We describe its potentials, as well as some of the foreseen obstacles related essentially to its use in preventive medicine.