The development of a surgical technique that removes the tumour and all local draining nodes in an intact package, namely total mesorectal excision (TME) surgery, has provided the impetus for a more selective approach to the administration of preoperative therapy. One of the most important factors that governs the success of TME surgery is the relationship of tumour to the circumferential resection margin (CRM). Tumour involves the CRM in up to 20% of patients undergoing TME surgery, and results in both poor survival and local recurrence. It is therefore clear that the importance of the decision regarding the use of pre-operative therapy lies with the relationship of the tumour to the mesorectal fascia. In addition, a high-spatial-resolution MRI technique will identify tumours exhibiting other poor prognostic features, namely, extramural spread >5 mm, extramural venous invasion by tumour, nodal involvement, and peritoneal infiltration. The potential benefits of a selective approach using MRI-based selection criteria are evident. That is, over 50% of patients can be treated successfully with primary surgery alone without significant risk of local recurrence or systemic failure. Of the remainder, potentially dramatic improvements may be achieved through the use of intensive and targeted preoperative therapy aimed not only at reducing the size of the primary tumour and rendering potentially irresectable tumour resectable with tumour-free circumferential margins, but also at enabling patients at high risk of systemic failure to benefit from intensive combined modality therapy aimed at eliminating micrometastatic disease.