Aimed to increase recombinant quality and solubility, co-production of individual chaperones or chaperone sets has been a common strategy since the role of these proteins in quality control has been solved, mainly involving protein holding to prevent aggregation, folding or refolding activities and disaggregation from inclusion bodies. Many studies report on the positive effects of chaperone gene co-expression, regarding solubility, yield, secretion ability and specific activity (green box). However, it is also true that this strategy has been largely controversial and the eventual success seen as highly product- and/or process-dependent. Also, more recent studies reveal that an excess of certain chaperones has negative effects on protein yield and other parameters related to protein quality (red box), mainly due to the role of chaperones in promoting proteolysis of folding reluctant proteins. This promotion of proteolysis seems to be mechanistically linked to the disaggregation activities ruled by DnaK [21, 77].