Patients with T4 rectal cancer may be increasingly defined by the use of pelvic MRI. This approach has the potential to classify patients who have tumour extending beyond the mesorectal fascia and those very close to but not beyond the mesorectal fascia (for example 1-2 mm). Prospective studies of MRI are required to validate such an approach. It is important that the full extent of local disease is defined prior to the commencement of radiation. Assessment after radiation is much more difficult. Even if tumour regression has occurred, if invasion of another organ was originally present, then surgical removal is required as only a small minority of patients will have a histopathologically complete response after CRT. Many investigators are developing improved CRT regimens that integrate either oxaliplatin or irinotecan with a fluoropyrimidines and radiation. There are two choices that allow intensification of pre-operative radiation. One approach is to escalate the dose of radiation and the other is to exploit the interaction between chemotherapy and radiation by adding more chemotherapy during the period of irradiation. Current interest predominantly is focused on the latter approach. Future studies are likely to assess agents directed against molecular targets. Careful consideration is required to define the best end points for successful pre-operative chemo-radiation leading to surgical excision.