Each cell hosts thousands of proteins that vary greatly in abundance, structure, and chemical properties. To ensure that all proteins are biologically active and properly localized, efficient quality control systems have evolved. While the structure, function, and regulation of some individual protein folding factors and proteases were resolved up to atomic resolution, others remain poorly characterized. In addition, little is known about which factors are required for viability under specific stress conditions. We therefore determined the physiological implications of 15 factors of the E. coli cell envelope by an integrated genetic approach comprising phenotypic analyses. Our data indicate that surA and tsp null mutations are a lethal combination in rich medium, that surA dsbA and surA dsbC double mutants are temperature sensitive, and that surA ptrA, surA yfgC, dsbA fkpA, degP tsp, degP ppiD, tsp ppiD, and degP dsbA double mutants are temperature sensitive in rich medium containing 0.5 M NaCl, while degP dsbA, degP yfgC, tsp ydgD, and degP tsp double mutants do not grow in the presence of SDS/EDTA. Furthermore, we show that in degP dsbA, degP tsp, and degP yfgC double mutants a subpopulation of LamB exists as unfolded monomers. In addition, dsbA null mutants expressed lower levels of the outer membrane proteins LptD, LamB, FhuA, and OmpW while FhuA levels were reduced in surA single and degP ppiD double mutants. Lower FhuA levels in degP ppiD strains depend on Tsp, since in a tsp degP ppiD triple mutant FhuA levels are restored.