Expression vectors, gene amplification, gene and production stability, cell line robustness, responsiveness to productivity enhancers, scalability, definable media - these are just a few key topics that have kept scientists, engineers and managers on their toes while the volumetric productivity from CHO cells has increased 100 fold during the last 20 years. The talk will try to summarize crucial insights and distinguish between claimed and true contributions from the various fields touched upon in the list of the above items for the rapid progression towards grams and now tens of grams per liter of recombinant proteins in high yielding processes. Most surprisingly, while undeniable progress has been made - a profound understanding of the cell host and in the (upstream) production process in making recombinant proteins in mammalian cells is still lacking. In solving the most obvious areas of "mystery" are great opportunities to move forward to the next level...