Proteins damaged by stressors such as heat, oxidizing conditions or toxic agents are deleterious to cells and must be properly taken care of. Accordingly, misfolded proteins trigger a cellular stress response that aims to either repair defective polypeptides or eliminate faulty elements when salvage is not possible. This stress response provides time for additional stressor-specific pathways that adapt the cell to the changed environment if necessary. Recent studies have investigated how proteins that frustrate the folding machinery are recognized and cleared from the cell. Surprisingly, these clearance mechanisms are not restricted to the protein level. The stress response can also eliminate the mRNA of polypeptides that are refractory to folding.