Total neoadjuvant therapy (TNT) for rectal cancer is the preoperative delivery of radiation or chemoradiotherapy as well as systemic chemotherapy for the purpose of improving treatment completion rates and decreasing toxicity, maximizing the primary tumor response, and improving survival for patients with rectal cancer. This review summarizes the data surrounding TNT, including several recent randomized controlled trials. Moreover, it reviews the literature regarding high-quality surgery and the role of radiation and chemotherapy in the treatment of rectal cancer in the modern era. Finally, it presents an evidence-based protocol for the selective use of TNT in the treatment of patients with rectal cancer.