Although surgery and radiotherapy are highly efficient in local tumor control, distal metastases and tumor recurrence often limit therapeutic outcome. It is becoming progressively more evident that curative tumor therapy depends on the presence and maintenance of an intact immune system which has the capacity to elicit cytotoxic effector functions against circulating tumor cells and distant metastases. Heat shock proteins (HSPs, also termed stress proteins) are involved in antigen processing and presentation and can act as "danger signals" for the adaptive and innate immune systems. This article reviews current knowledge relating to the induction and manifestation of stress protein-related immunological responses that are pertinent to the development and maintenance of protective anti-tumor immunity.