Ethanol fermentations were established industrial process in late 19th and early 20th century prior to the formal genesis of chemical engineering, but the acetone-butanol-ethanol fermentation in the 1910s coincides with the evolution of chemical engineering as a distinct discipline. Chemical engineers however had their most profound impact in the mid 1940s in resolving the botttleneck for the development of large-scale, oxygenated, deep-tank fermentations for antibiotic production. This effort and the classical now work by Elmer Gaden and co-workers constitutes the foundation of biochemical engineering as a distinct sub-discipline. The late 1950s and 1960s brought to fore a wealth of new challenges and ideas with the concepts of bioreactors for immobilized enzymes and cells for biotransformations and whole-cell biocatalysis, in addition to the concept of computer-controlled fermentors. The 1970s saw an explosion of ideas on new bioreactor designs (including the various air-lift designs, many of which are now widely used), and numerous bioreactor-operation policies and their optimization including the now widely employed concept of fed-batch fermentations. The 1980s were marked by the realization that the design of bioreactors for growing animal cells (whether on microcarriers or in free suspension) was a new major challenge that required fresh analysis and new mixing concepts and scale up. This challenge was met with characteristic success leading to the growth of the now dominant animal-cell biotechnology for the production of protein therapeutics. This was followed by more specialized challenges at smaller scales to develop bioreactors for tissue engineering applications, and scaled-down technologies for the development of small or microbioreactors for parallel or high-throughput bioprocessing. Now, as we face the urgency to develop sustainable technologies for the production of chemicals and biofuels from renewable resources, there is a fresh set of challenges for efficient bioreactors and processes to meet perhaps the most diverse set of needs and applications.