Over the years, plant cells and hairy roots have been established as a successful and viable alternative for production of bioactive secondary metabolites and recombinant proteins, replacing the use of whole plants. Bioreactors are used for continuous and consistent in vitro production of these low-volume high-value bioactive/therapeutic molecules from plant cells and hairy roots at large scale. The design and operation of bioreactors for plant cell and hairy root cultivation differs from well-established microbial cultivation due to their size, aggregation, sensitivity to hydrodynamic stress, and viscous nature of the culture broth. The choice of bioreactor and nutrient feeding strategies to overcome substrate limitation and inhibition can be instrumental in enhancing the biomass and product productivity in plant cell and hairy root cultivations at large scale. Hence, this chapter deals briefly with the design and development of bioreactors to achieve maximum productivity in plant cell and hairy root cultivations. The overview of reactor operating parameters considered while designing bioreactors for plant cells and hairy roots are discussed. The chapter also includes application of mathematical modeling to optimize the design of bioreactors and in silico prediction of nutrient feeding strategies during fed-batch and continuous mode of bioreactor cultivation. © Springer Nature Singapore Pte Ltd. 2018.