Despite breakthroughs in molecular biology that have opened up new synthesis routes to pharmaceuticals and fine chemicals, biotechnology has not been widely deployed for production of high volume, low cost chemicals. It is argued that the pace of development for large-scale bioprocesses can be accelerated by increasingly applying basic principles of chemical engineering together with front line concepts of molecular biology. A fundamental understanding of the coupling between kinetic, hydrodynamic, and transport processes in a bioreactor may also favorably impact process economics. The status and future opportunities in areas such as bioreaction kinetics, reactor selection, design, scale up and control are discussed. Several examples of how reaction engineering principles can lead to successful design and scale up and avoid common pitfalls are illustrated. Finally, the need to optimize the integrated process, rather than just the bioreactor, is indicated.