Treatment of retroperitoneal soft tissue sarcomas is a difficult clinical problem. Despite the improvement in resection rates in the most recent surgical series, local control still remains the main problem because of the high incidence of local recurrences after surgery. Postoperative radiation therapy has not been always successful because of dose-tolerance of surrounding normal structures, which prevent the delivery of adequate doses of radiation. To overcome this limitations, new therapeutic approaches including external-beam radiation and intraoperative radiation therapy (IORT) have been evaluated at some Institutions. The results of IORT with or without external-beam radiation are reviewed and our experience with preoperative radiation and IORT is reported. As treatment of retroperitoneal sarcomas has evolved into combined modalities including preoperative radiation, maximum surgical resection and IORT, a possible improvement in local control rates has been achieved. However, locoregional failures and the incidence of distant metastases remain a challenge, emphasising the need for further improvement in local and distant treatment. The new phase II trial, activated within the Italian Sarcoma Group, with preoperative concurrent chemo-radiation therapy and IORT is presented.