The optimal type of neoadjuvant therapy regimen in rectal cancer is contentious.This study aimed to review the impact of neoadjuvant therapy on oncological outcomes and complications (short and long term) in patients undergoing total mesorectal excision for rectal cancer.An electronic search of MEDLINE, PubMed, EMBASE, and the Cochrane Database of Collected Reviews was performed through March 2010.Key-word combinations including rectal cancer, total mesorectal excision, radiotherapy, chemotherapy, endorectal ultrasound, and magnetic resonance imaging were used to identify randomized control trials where chemotherapy and/or radiotherapy were deployed before resectional surgery.Patients underwent total mesorectal excision for rectal cancer who did and did not receive preoperative chemotherapy and/or radiotherapy.The main outcome measures comprised the impact of the addition of neoadjuvant therapy to total mesorectal excision on the perioperative complication rate, the pathological complete response rate, the rate of local recurrence, and long-term treatment-related complications.A total of 12 randomized control trials involving 9410 patients were included. Both short-course radiotherapy and long-course chemoradiation can offer a relative risk reduction of 50% in local recurrence in appropriately selected patients with stage II and III rectal cancer. This oncological benefit comes at the cost of a relative risk increase of 50% in both acute treatment-related toxicity and long-term anorectal dysfunction.Preoperative staging provides only an estimate of the "true" tumor stage that can only be determined by histological assessment of the tumor specimen which renders appropriate patient selection challenging.The current treatment trade-off of a relative risk reduction of local recurrence of 50% at the cost of a relative increase of 50% in treatment-related complications underpins the need for more accurate patient staging and more precise delivery of neoadjuvant therapy.