Rectal cancer is one of the most common neoplasms of Western Countries. Overall mortality at 5 years is about 40%. This cancer is commonly diagnosed at a precocious stage, but because of local relapse and/or metastatic disease, only half of radically resected patients can be considered disease free. The value of adding radiotherapy to surgery in the treatment of patients with resectable rectal cancer has been assessed in trials using either preoperative or postoperative irradiation. Preoperative irradiation is more "dose-effective" than postoperative radiotherapy; that is, a higher dose is needed postoperatively to reduce rates of local recurrence to the same extent as preoperative radiation. Nevertheless, preoperative treatment has not been routinely recommended, mainly because it has not been shown to improve overall survival and because in some trials it has been associated with increased postoperative mortality. This paper critically reviews clinical trials of chemoradiotherapy on whether an optimal combination exists for locally advanced rectal cancer. Even if in the latest years, recent advances in surgery have improved the local control of disease, the next steps in rectal cancer care should aim at the improvement of local cure rates and the enhancement of systemic control. New approaches to CT treatment are necessary. Patient enrollment into rigorous and well-conducted clinical trials will generate new information regarding investigational therapies and it will offer improved therapies for patients with this disease.