**1. Introduction**

Rectal cancer continues to affect many patients in the United States and world-wide. For instance, in 2012, rectal cancer affected 40,290 Americans [1]. Patients affected with rectal cancer who have a clinical stage II (T3-T4, NO, MO) or III (Any T, N1-N3, M0) tumor are treated with pre-operative chemoradiation (CRT) followed by surgical intervention [total mesorectal excision (TME)]. In up to 40% of patients treated with CRT, the tumor becomes clinically undetectable (cCR) [2]. Clearly, this is a desirable outcome in oncology. Adding novel radiosanitizing agents, prolonging the period from CRT to TME, increasing the radiation dose, adding chemotherapy before CRT are few modalities that have been investigated to increase the number of patients achieving a complete response. The following chapter reviews current strategies in recent attempts at maximizing the ratio of patients who achieve a cCR. Current margins are resection following TME in the era of CRT are also reviewed.
