Plants and their rich variety of natural compounds are used to maintain and to improve health since the earliest stages of civilization. Despite great advances in synthetic organic chemistry, one fourth of present-day drugs have still a botanical origin, and we are currently living a revival of interest in new pharmaceuticals from plant sources.

Modern biotechnology has defined the potential of plants to be systems able to manufacture not only molecules naturally occurring in plants but also newly engineered compounds, from small to complex protein molecules, which may originate even from non-plant sources. Among these compounds, pharmaceuticals such as vaccines, antibodies and other therapeutic or prophylactic entities can be listed. For this technology, the term plant molecular farming has been coined with reference to agricultural applications due to the use of crops as biofactories for the production of high-added value molecules. In this perspective, edible plants have also been thought as a tool to deliver by the oral route recombinant compounds of medical significance for new therapeutic strategies. Despite many hurdles in establishing regulatory paths for this “novel” biotechnology, plants as bioreactors deserve more attention when considering their intrinsic advantages, such as the quality and safety of the recombinant molecules that can be produced and their potential for large-scale and low-cost production, despite worrying issues (e.g. amplification and diffusion of transgenes) that are mainly addressed by regulations, if not already tackled by the plant-made products already commercialized. The huge benefits generated by these valuable products, synthesized through one of the safest, cheapest and most efficient method, speak for themselves.

Milestone for plant-based recombinant protein production for human health use was the approval in 2012 by the US Food and Drug Administration of plant-made taliglucerase alfa, a therapeutic enzyme for the treatment of Gaucher’s disease, synthesized in carrot suspension cultures by Protalix BioTherapeutics.

In this review, we will go through the various approaches and results for plant-based production of proteins and recent progress in the development of plant-made pharmaceuticals (PMPs) for the prevention and treatment of human diseases. An analysis on acceptance of these products by public opinion is also tempted.