Over the last two decades the recombinant production of therapeutic and industrially important proteins has gained more attention due to a dramatically increased demand. This has driven the effectual bioprocess development to maximize the yield. Thus several microbial, mammalian, and insect expression hosts have been improved. Among the microbial hosts, Escherichia coli and yeast systems are widely used for the production of most of the therapeutic proteins. Further, advances in media and process optimization technologies, such as scale-out technology, process analytical technology, high throughput process devices, and modern bioreactors have enabled a many fold improvement in the final yield. In addition to this, several computational tools and simulation models have been developed to achieve higher product yield. This chapter basically outlines the different important expression systems, their advantages and disadvantages, and the modern bioprocess technologies used for protein production.