GRP94 is the ER representative of the HSP90 family of stress-induced proteins. It binds to a limited number of proteins in the secretory pathway, apparently by recognizing advanced folding intermediates or incompletely assembled proteins. GRP94 also binds peptides and can act as a tumor vaccine, delivering the peptides for presentation to T lymphocytes. Here, we review the current data about GRP94 and propose a structural model that integrates the biochemical data and known functions of the protein.