Although several modalities have been discussed, a comprehensive intraoperative program should have IOERT, IOHDR, and perioperative brachytherapy facilities available to treat all sites. Interstitial brachytherapy is preferable for the treatment of gross residual tumor; IORT (IOERT for accessible sites and IOHDR for poorly accessible sites) is added to irradiate intraoperatively the surrounding margins after gross resection; and fractionated EBRT could be used in moderate doses post-operatively to irradiate the entire area of potential microscopic disease. Depending on the volume and location of the tumor, and the available expertise and equipment, IOERT, IOHDR, or perioperative brachytherapy could be used along with EBRT and surgery for the optimal management of malignancies. Finally, the best results of IOHDR are obtained when used as a conformal boost to the tumor bed after resection in conjunction with supplementary EBRT.