It is now well established that the clinical behaviour of many human cancers is determined by molecular interactions between the malignant cells and the environment in which they exist. Abnormal blood vessels that arise from aberrant angiogenesis are an important cause of tumour hypoxia, which stimulates further angiogenesis and leads to radioresistance, altered repair of DNA damage and changes in the expression of genes important in tumour progression and metastasis formation. In addition, the abnormal tumor vessels contribute to high interstitial fluid pressure (IFP), an important predictor of reduced survival in women receiving radiotherapy for cervix cancer and a barrier to drug penetration. These and other aspects of the abnormal microenvironment in tumors, while conferring poor prognosis and impeding the effectiveness of currently available treatments, also present unique opportunities for improving cure rates. Combinations of radiotherapy or chemotherapy with novel molecular treatments that target angiogenesis or hypoxia are the focus of ongoing laboratory and clinical studies. Mathematical models of how these treatments interact can generate new hypotheses for laboratory and clinical testing, inform the design of future studies with respect to important issues such as optimal dosing and sequencing of the various treatments, and help to explain unexpected preclinical or clinical findings.