Heat shock proteins are present in almost all intracellular compartments and serve by folding newly synthesized proteins, disassembling unstable proteins, and assisting in the transportation of proteins within the cell. Under certain circumstances they are also present on the cell surface, and can be shed or secreted into the extracellular environment. Although they possess many functional roles, their ability to stimulate innate and antigen-specific immunity have made them attractive candidates for vaccine development. Here, we review some of the approaches that have been used to genetically engineer molecular chaperones for their secretion from tumor cells or targeting them to the plasma membrane of such cells in order to promote anti-tumor responses. Treatment of tumor cells engineered to secrete or display chaperones may be of benefit, particularly in the area of cell-based vaccine development.