Molecular chaperones are abundant, well-conserved proteins responsible for the maintenance of the conformational homeostasis of cellular proteins and RNAs. Environmental stress is a proteotoxic insult to the cell, which leads to chaperone (heat shock protein, stress protein) induction. The protective role of chaperones is a key factor for cell survival and in repairing cellular damage. The present review summarizes our current knowledge about changes in chaperone expression and function in the aging process, as well as their possible involvement in the development of longevity and cellular senescence. We also overview their putative role in neurodegenerative diseases, such as in Alzheimer's disease and the changes in immune and autoimmune response against various chaperones in aging.