Hsp90 and small Hsps are two abundant types of eukaryotic stress protein whose function has remained largely enigmatic. In the cell, Hsp90 exists in a complex (with other Hsps and prolyl isomerases) possibly implicated in interactions with non-native proteins. Recent biochemical analysis of both Hsp90 and small Hsps has revealed that they may act as ATP-independent molecular chaperones involved in protein folding and unfolding events.