In the last three decades, protein yields from recombinant CHO cells in bioreactors have increased 10-100 fold, as the result of improvements in media, bioprocess design and cell culture process control. The contribution of expression vector constructs and host cell engineering is, contrary to what numerous publications and even recent reviews are claiming, minor. The academic world has been very active in solving perceived problems in CHO technology by addressing them mostly through cell engineering. The industry however was bound to conservative approaches typical in pharmaceutical manufacturing and by the benefit of “sticking to things that worked.” Significant investments (cell banking, testing, established operational handlings) into a relatively solid approach with proven track records from a non-modified cell host could not easily be abandoned just because a cell cycle gene or an anti-apoptotic gene might eventually provide some (minor) benefit. In fact, the historic (proprietary) body of knowledge concerning a given cell host provided ample opportunity to reap the benefits from modifications and significant enrichments of media formulation and improvements in process strategy and control, with resultant dramatic improvements. In general, the same vector components are used today as 20 years ago. Codon-optimization of gene sequences for the desired protein-of-interest have improved overall expression of some proteins, but did not result in “break-through” yield increases. The identification and selection of suitable clonal populations from transfected cells is now facilitated by widely accessible and cost-efficient equipment that allows high-throughput screening, including the use of flow-cytometry and sorting. Some DNA elements in plasmids and novel vector/gene-transfer approaches have pushed primary expression higher. Currently marketed protein therapeutics are exclusively produced in large-volume steam-sterilizable, stainless steel bioreactors, and the majority of production processes therein can be characterized as “fed-batch” cultures, with processing times of 10-20 days. Over the last 10 years a strong “disposable” trend has emerged, particularly with innovative products that are entering the clinic, but also with “biosimilar” products under development. “Single-use bioreactors” (SUB), pre-sterilized plastic bags, mounted into or onto containers or platforms, serve as a physical barrier between the non-sterile environment and cell culture process liquids. While stirring with marine and pitched blade impellors is still the main method for mixing of both sterilizable stainless steel and single-use bioreactors, other impeller-free approaches have emerged as well that are now applied in single use bioreactors. The largest stirred SUB bioreactors have working volumes of up to 2,000 Liters, the largest prototype disposable bioreactor, being a non-stirred “OrbShake” SUB (Kühner AG, Birsfelden, Switzerland) possesses a working volume of 2,500 L.