Neoadjuvant chemoradiation (CRT) is standard treatment for stage II–III rectal cancer. Fluoropyrimidine-based CRT prolongs disease-free survival over adjuvant CRT and improves local control over both adjuvant CRT and neoadjuvant radiotherapy alone, but does not prolong overall survival. New approaches to neoadjuvant therapy may improve outcome in this disease. Oxaliplatin, a standard component of chemotherapy for the treatment of both resected and metastatic colon cancer, is a potent radiosensitizer with synergistic radiosensitizing activity in combination with 5-FU in preclinical studies. Early clinical trials showed promising activity with the addition oxaliplatin to 5-FU–based CRT in stage II–III rectal cancer; however, early data from phase III trials seem to be disappointing. This article reviews the existing literature and explores the potential role of oxaliplatin as part of neoadjuvant CRT for rectal cancer.