Subunit vaccines are based on isolated pure or semi-pure microorganism components (antigens). As compared to traditional formulations based on whole pathogens (killed or attenuated), these vaccines are safer even if unable per se to boost immune responses unless supplemented by adjuvants. Nowadays, thanks to the development of high-performance gene engineering and biochemical procedures, subunit-based vaccines emerging on the market are formulated with recombinant antigens produced in bacterial, yeast or animal cells. Plant-based expression systems are turning out to be very attractive “biofactories” of recombinant antigens as well, since they ensure low-cost, rapid and easy manufacturing scaling up and intrinsic biosafety of the final product. Nevertheless, also plant-produced recombinant antigens are per se poorly immunogenic. A few attempts to set-up strategies to obtain self-adjuvanted immunogens from plants have been made. This chapter will be mainly focused on the possibility to exploit to this aim plant heat-shock proteins. © Springer International Publishing Switzerland 2014. All rights reserved.