Recombinant mammalian cells are used to produce numerous, high-value protein therapeutics. Generating hyper-producing cell lines is crucial for delivery of products to ailing patients. Better understanding of the complex trait of hyperproductivity can facilitate the creation of hyper-producing cell lines. Ruminating over the reported transcriptomic and proteomic studies, we attempt to assess whether high productivity response is a result of minute changes occurring globally or large alterations observed locally at the molecular level. We present here our philosophical perspective on the alternative routes to high productivity. We contend that given the advances in genome-scale technologies and data analysis approaches, insights gained from elucidating the gene–trait relationship underlying hyperproductivity will accelerate the development of hyperproductive processes.