Escherichia coli has been the most popular cellular biofactory for the production of many biomolecules including recombinant proteins whose bioactivities are not dependent on complicated post-translational modifications such as glycosylation. Despite many advantages of protein production using E. coli, the formation of insoluble inclusion bodies (IBs) poses a major challenge to harnessing E. coli as a host of choice. Furthermore, the complicated processing steps associated with 113 extraction, solubilisation of IBs and refolding of the solubilised-denatured 113 proteins, which are typically encountered in the traditional 113 processing flowsheet, significantly compromise process economics of IB-route protein production using E. coli. In this paper, many recent advances in innovative IB processing technologies are reviewed with a special emphasis on their potential to contribute to process intensification, which is critical to achieve better process economics in the IB-route recombinant protein production using E. coli. (c) 2005 Published by Elsevier Ltd.