The production of secondary metabolites, and more specifically alkaloids, from medicinal plants is still an important objective for many research programs. When natural lead compounds have been discovered and when chemical synthesis cannot be easily performed, the extraction and purification of biomolecules from entire plants is generally the preferred solution. However, it is now established that plant cells and tissue cultures in bioreactors can constitute an alternative solution to this agronomical approach. Our research programs devoted to the production of tropane alkaloids from Datura innoxia and furanocoumarins from Ruta graveolens have shown that hydroponics and aeroponics, techniques situated in-between field and fermentor scales, enable the entire plants to be used as efficient bioreactors. Revisiting scientific advances made in the past decades, the ethical, legal, biological and technological aspects are discussed in the light of the most recent literature, in order to establish a roadmap for further developments of plant secondary metabolite production systems.