In Western countries, colorectal cancer is the third most common cancer in terms of incidence and mortality. The management of rectal cancer has undergone and continues to undergo significant evolutions. In the last two decades, new multimodality strategies have been developed. Multimodality treatments have improved the prognosis of locally advanced rectal cancer with local recurrences decreasing from 40% to < 10% and overall survival increasing from 50% to 75% in the last 40 years. This review discusses the role of neoadjuvant chemoradiotherapy regimens used in the standard combined modality treatment programs for rectal cancer and focuses on the ongoing research to improve these regimens.