The standard adjuvant therapy for resectable T3 and/or N1-2 rectal cancer is pelvic radiation therapy plus fluorouracil (5-FU)-based chemotherapy. Two randomized intergroup trials, INT 0114 and INT 0144, will help determine the ideal chemotherapeutic agents and their routes of administration in the postoperative setting. The randomized National Surgical Adjuvant Project for Breast and Bowel Cancers trial NSABP R-03 and the INT 0147 trial will compare the efficacy and functional results of the preoperative and postoperative combined-modality therapy approaches. The delivery of effective therapies, as well as the development of more innovative approaches, is enhanced by a multidisciplinary collaboration among medical, surgical, and radiation oncologists.