Mitochondrial protein homeostasis is crucial for cellular health, and perturbations have been linked to a plethora of human diseases. Proteostasis is maintained mainly by a network of mitochondrial chaperones and proteases, that assist in protein folding and degrade nonfunctional or superfluous proteins. Upon proteomic imbalances or defects in mitochondrial functions, protective cellular responses are activated to restore and maintain organellar integrity. This viewpoint describes our current knowledge and understanding of these protective pathways and addresses open questions and perspectives in the field of mitochondrial stress responses.