Patients with high-risk soft tissue sarcomas (STS)-FNCLCC grade 2-3, size >5 cm, deep to the fascia-are at risk for developing local recurrence and distant metastasis despite surgical tumor resection. Therefore, the management of high-risk STS requires a multidisciplinary approach. Besides surgery, radiotherapy, and chemotherapy, regional hyperthermia (RHT) has the potential to become the fourth standard treatment modality for the treatment of these patients. RHT means non-invasive selective heating of the tumor area to temperatures within the range of 40-43°C for 60 min by the use of an electromagnetic heating device. Thereby RHT is always applied in addition to radiotherapy or chemotherapy or both but is not effective as a single treatment. Beside direct cytotoxicity, RHT in combination with chemotherapy enhances the drug cytotoxicity mainly by increased chemical reaction and intratumoral drug accumulation. For the neoadjuvant setting, RHT in combination with a doxorubicin- and ifosfamide-based chemotherapy has been shown to dramatically improve the tumor response rate but also prevents from early disease progression as compared to chemotherapy alone. The addition of RHT to a multimodal treatment of high-risk STS consisting of surgery, radiotherapy, and chemotherapy either in the neoadjuvant setting but also after incomplete or marginal tumor resection has been shown to significantly improve local recurrence- and disease-free survival. Based on these results and in conjunction with the low RHT-related toxicity, RHT combined with preoperative or postoperative chemotherapy should be considered as an additional standard treatment option for the multidisciplinary treatment of locally advanced high-grade STS.