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Treatment modalities in rectal cancer have undergone a slow, evolutionary transition over the past 30 years. More recently, contemporary descriptions of advanced preoperative chemotherapy and radiation schema have led to a rapid revolution in the management of this disease. In this review we focus on current evidence-based neoadjuvant strategies used in the treatment of locally advanced rectal cancer and metastatic rectal disease. Finally, we provide a foundation for discussion of still unresolved issues.