The last twenty years have seen remarkable progress, both in the number of recombinant biopharmaceuticals and in the technology to produce them. The scene had already been set in the previous two decades with important studies defining the nutritional requirements, and conditions for growth in bioreactors, of several mammalian cell types. The early commercial drivers for cell culture development were human and veterinary vaccines and a handful of non-recombinant proteins. The introduction of monoclonal antibody technology in the 1970s provided a fresh impetus for large scale mammalian cell technology initially for diagnostic reagents such as blood grouping reagents and subsequently for therapeutic products. Fed-batch culture techniques, developed during this period in airlift reactors were subsequently applied to the production of recombinant proteins in both airlift and stirred systems. Over the last twenty years the required quantities of therapeutic proteins, particularly monoclonal antibodies, have increased enormously driving increases in reactor numbers and scale (up to 20,000 litres) and improvements in productivity of 100 fold. These improvements have resulted from the introduction of highly efficient gene expression technology such as the GS (glutamine synthetase) system, improved host cell lines and improved feeding strategies for fed-batch culture. For monoclonal antibodies, titres of grams/litre are now achieved routinely in chemically defined media and seem set to increase, particularly as our knowledge of the biology underpinning productivity improves.