Over the past decade, we have gained substantial new insight into the overall behavior of the PN and the molecular mechanics of its components. Advances in structural biology and biophysical approaches have allowed chaperone mechanisms to be interrogated at an unprecedented level of detail. Recent work has provided fascinating insight into the process of protein folding on the ribosome and revealed how highly allosteric chaperones such as the heat shock protein 70 (Hsp70), Hsp90, and chaperonin systems modulate the folding energy landscapes of their protein clients. Studies of chaperone systems from bacteria and eukaryotes have revealed common principles underlying the organization of chaperone networks in different domains of life. Recently, we have begun to appreciate the relative complexity of eukaryotic chaperones and are starting to understand how eukaryotes deal with the challenge of folding a large proteome enriched in multidomain proteins.