The current management of rectal cancer in the preoperative setting provides a unique opportunity to explore individualized patient care. The management of adenocarcinoma of the rectum must involve a multidisciplinary approach. The distinctive feature of rectal tumors to either achieve complete resolution or no response in patients submitting to the same treatment modalities demonstrates that the biology of rectal tumors requires further insights. An understanding of the biology of rectal tumors might permit for selection of patients with an aggressive phenotype allowing for alterations in the operative and neoadjuvant planning. The critical concepts in the oncogenesis of rectal cancer are areas of dynamic progression and require constant assessment.