A series of clinical trials in the last several decades has resulted in the development of multimodality treatment of locally advanced rectal cancer that includes neoadjuvant (preoperative) chemoradiotherapy, total mesorectal excision, and postoperative adjuvant chemoradiotherapy. Owing to this regimen, patients with locally advanced rectal cancer have better survival rates than patients with colon cancer, but at the cost of substantial morbidity and reduced quality of life. The challenge is to identify treatment approaches that maintain or even improve oncologic outcomes while preserving quality of life. We have identified different tumor characteristics that are associated with recurrence and probability of survival for locally advanced rectal cancer. This risk stratification, based on baseline clinical staging and tumor response to chemoradiotherapy, has led us to question whether all patients with locally advanced rectal cancer require every component of the multimodal regimen. In this article, we will review recent evidence that some patients with locally advanced rectal cancer can be spared one or more treatment modalities without compromising long-term oncologic outcomes and while preserving quality of life.