Rectal cancer treatment presents a challenge, and its optimal management requires a multidisciplinary approach involving surgical, medical, and radiation oncologists. Advances in surgical techniques, radiotherapy, and medical imaging technology have transformed the therapeutic landscape and have led to substantial improvements in both local disease control and patient survival. The currently established standard of care for patients with locally advanced rectal cancer involves preoperative (neoadjuvant) concurrent radiotherapy and infusional fluorouracil-based or oral capecitabine-based chemotherapy, also known as chemoradiotherapy (CRT), followed by surgery. Surgery is often followed by adjuvant chemotherapy. Here we discuss the evolution of standard therapy for rectal cancer patients and the use of preoperative CRT for the treatment of locally advanced disease. Treatment schemes that have attempted to broaden the horizons of standard therapy include the use of induction chemotherapy and "watch-and-wait" approaches. We examine several novel trials using these and other treatment approaches, which may eventually lead to better patient selection and the avoidance of overtreatment and unnecessary adverse effects.