Bioreactors of various forms have been widely used in environmental protection, healthcare, industrial biotechnology, and space exploration. Robust demand in the field stimulated the development of novel designs of bioreactor geometries and process control strategies and the evolution of the physical structure of the control system. After the introduction of digital computers to bioreactor process control, a hierarchical structure control system (HSCS) for bioreactors has become the dominant physical structure, having high efficiency and robustness. However, inherent drawbacks of the HSCS for bioreactors have produced a need for a more consolidated solution of the control system. With the fast progress in sensors, machinery, and information technology, the development of a flat organizational control system (FOCS) for bioreactors based on parallel distributed smart sensors and actuators may provide a more concise solution for process control in bioreactors. Here, we review the evolution of the physical structure of bioreactor control systems and discuss the properties of the novel FOCS for bioreactors and related smart sensors and actuators and their application circumstances, with the hope of further improving the efficiency, robustness, and economics of bioprocess control.