Medicinal plants are sustainable bio-factories for valuable active pharmaceutical ingredients (API). They are commonly grown in the field and their extracts have a given combination of constituents. There is some variation due to climate fluctuations and plant diseases (microbial infections), genotypic changes, soil differences, etc. Additionally, fertile agricultural areas are increasingly limited. However, these variations are undesired because they are non-controllable and can affect the batch conformity of a drug significantly. This is a challenge for producers of phyto-pharmaceuticals, and the variations in the API composition are compensated by mixing extracts from various batches to achieve the required continuous quality of an authorized drug. These drawbacks of field cultivation are overcome by well-defined bioreactor-based cultivation. Biomass growth and API production take place under variable but controllable cultivation conditions, resulting in customized extracts. Variation of the cultivation conditions leads to qualitative and/or quantitative changes in the metabolome. During bioreactor cultivation, plant cells tend to stay connected after division, which leads to the formation of aggregates. The size of shear-sensitive plant cell aggregates influenced by hydrodynamic forces resulting from mechanical agitation was often recognized as an intangible parameter, which might be responsible for general variability in plant cell culture processes. To date, however, the bioreactor approach is not often industrially implemented. This chapter provides an overview of the challenges in the cultivation of plant cell systems, briefly illustrated by (i) research on Hypericum perforatum tissue cultures into up-to-date approaches for production of hyperforin and hypericin, possibly functional at a pre-commercial level in the future, and (ii) effects of hydrodynamic mechanical forces on Taxus chinensis submerged cultures for production of paclitaxel.