The biological functions of proteins are governed by their three-dimensional 
fold. Protein folding, maintenance of proteome integrity, and protein 
homeostasis (proteostasis) critically depend on a complex network of molecular 
chaperones. Disruption of proteostasis is implicated in aging and the 
pathogenesis of numerous degenerative diseases. In the cytosol, different 
classes of molecular chaperones cooperate in evolutionarily conserved folding 
pathways. Nascent polypeptides interact cotranslationally with a first set of 
chaperones, including trigger factor and the Hsp70 system, which prevent 
premature (mis)folding. Folding occurs upon controlled release of newly 
synthesized proteins from these factors or after transfer to downstream 
chaperones such as the chaperonins. Chaperonins are large, cylindrical complexes 
that provide a central compartment for a single protein chain to fold unimpaired 
by aggregation. This review focuses on recent advances in understanding the 
mechanisms of chaperone action in promoting and regulating protein folding and 
on the pathological consequences of protein misfolding and aggregation.