Escherichia coli, is one of the most widely preferred organism for the production of recombinant protein. Most of the FDA approved therapeutic proteins are produced in E. coli. The well-established cell factory of E. coli makes it a perfect heterologous system of choice for the production of recombinant proteins. In recent years, several advances have been taken place for modifying these cell factories for easy production of therapeutic proteins with utmost precision. Several molecular tools and protocols are available in hand for the high level protein production in heterologous expression system. Adapting the best strategy for producing recombinant proteins in E. coli can be obtained using several approaches. Combination of strategies will work well to enhance the expression and stability of produced protein. In this review we try to collate different strategies and approaches that can enhance the production as well as the stability of proteins expressed in E. coli.