Therapy-inducible vectors are useful for conditional expression of therapeutic genes in gene therapy, which is based on the control of gene expression by conventional treatment modalities. By this approach, combination of chemotherapy, radiation or hyperthermia with gene therapy can result in considerable, additive or synergistic improvement of therapeutic efficacy. This concept has been successfully tested in particular for gene therapy of cancer. The identification of efficient heat-responsive gene promoters provided the rationale for heat-regulated gene therapy. The objective of this review is to provide insights into the cellular mechanisms of heat-shock response, as prerequisite for therapeutic actions of hyperthermia and into the field of heat-responsive gene therapy. Furthermore, the major strategies of heat-responsive gene therapy systems in particular for cancer treatment are summarized. The developments for heat-responsive vector systems for in vitro and in vivo approaches are discussed. This review will provide an overview for this gene therapy strategy and its potential for multimodal therapeutic concepts in the clinic.