Co-chaperonins function together with chaperonins to mediate ATP-dependant protein folding in a variety of cellular compartments. GroEL and its co-chaperonin GroES are the only essential chaperones in Escherichia coli and are the archetypal members of this family of protein folding machines. The unique mechanism used by GroEL and GroES to drive protein folding is embedded in the complex architecture of double-ringed complexes, forming two central chambers that undergo structural rearrangements as part of the folding mechanism. GroES forms a lid over the chamber, and in doing so dislodges bound substrate into the chamber, thereby allowing non-native proteins to fold in isolation. GroES also modulates allosteric transitions of GroEL. A significant number of bacteria and eukaryotes house multiple chaperonin and co-chaperonin proteins, many of which have acquired additional intracellular and extracellular biological functions. In some instances co-chaperonins display contrasting functions to those of chaperonins. Human Hsp60 continues to play a key role in the pathogenesis of many human diseases, in particular autoimmune diseases and cancer. A greater understanding of the fascinating roles of both intracellular and extracellular Hsp10, in addition to its role as a co-chaperonin, on cellular processes will accelerate the development of techniques to treat diseases associated with the chaperonin family.