The modern approach to cancer therapy involves combinations of surgery, radiation and drugs targeted against malignant tumour cells. However, expanding knowledge in the fields of angiogenesis and vascular biology over the last several years has led to the investigation of therapeutic strategies targeted to the vasculature (proliferating and non-proliferating endothelial cells) in combination with standard therapy. It is the objective of this review to describe the potential use of antiangiogenic therapy, targeted to the proliferating endothelium, from the point of view of the radiation oncologist. This review will describe the concept of a two-cell compartment model for tumours, with both the endothelial cells as well as the tumour cells being potential targets for radiotherapy. This review will then explore the promising evidence and rationale for combining antiangiogenic drugs and radiotherapy to enhance local control.