The treatment for high-risk soft-tissue sarcomas (STSs) in adults remains a challenge for the multidisciplinary approach. Despite aggressive local treatment, high-risk STSs have a tendency for hematogenous spread, which is related, for each histologically distinct sarcoma, to risk factors, such as pathologic grade, size and location. The multimodality approach focuses on the combination of radiochemotherapy in a neoadjuvant or adjuvant setting, surgery being considered the mainstay of local treatment. Therefore, current clinical research aims include preoperative treatment to control systemic microscopic disease and to downsize the primary tumor mass. Within the past 20 years, the application of hyperthermia has been integrated in multimodal treatment strategies in several forms of advanced malignant tumors, as well as in STSs. Hyperthermia is of clinical interest in the temperature range of 40-43 degrees C. Higher temperatures of 44-46 degrees C are not clinically realistic. The rationale for the combination of cytotoxic drugs with regional hyperthermia in the treatment of STS is based upon experimental and clinical evidence that heat increases the killing of tumor cells by direct thermal toxicity and enhances the efficacy of some drugs, such as alkylating agents and platinum analogs. Moreover, recent results show that hyperthermia may be able to modulate the immune system by inducing the expression of heat-shock proteins. The approach of multimodality treatment in STS has used regional hyperthermia with systemic chemotherapy within a preoperative and postoperative strategy. The synergistic effect of hyperthermia with chemotherapy is also used in locoregional treatments, such as isolated limb perfusion and intraperitoneal chemotherapy.