Integration of surgery and radiation (external beam, EBRT; intraoperative, IORT) has become more routine for patients with locally advanced primary cancers and those with local-regional relapse. This article discusses patient selection and treatment from a more general perspective, followed by a discussion of patient selection and treatment factors in select disease sites (pancreas cancer, colorectal cancer, retroperitoneal soft-tissue sarcomas). Outcomes with combined modality treatment (surgery, EBRT alone or with concurrent chemotherapy, IORT) are discussed. The ultimate in contemporary integration of radiation and surgery is found in patients who are candidates for surgery plus both EBRT and IORT.