The heat-shock proteins (HSPs) belong to a family of ubiquitous and abundant proteins used successfully in prophylactic and therapeutic vaccination against tumors. The HSPs are natural chaperones of peptides that reflect the immunologic composition of the cell. Immunization with tumor-derived HSP-peptide complexes (HSP-PC) induces a potent antigen-specific immune response against both the primary tumor and preestablished metastases; the response is restricted to the tumor from which the HSPs are purified. This article describes the manufacturing process of an individual HSP vaccine, and discusses the rationale, feasibility, advantages, and safety of this new approach of cancer immunotherapy in the context of various animal models and of the first HSP clinical trial.