The response of tumour cells to chemotherapy or radiotherapy is clearly dependent upon the inherent sensitivity of the cells to those agents. That sensitivity can, however, be markedly affected by the biochemical and physiological status of the tumour cell during treatment. In this review, a critique of the current evidence for, and the extent of, microenvironmental heterogeneity in tumours is presented. Its influence on radiation and chemotherapy is then examined, with examples from the author's studies with spheroids in vitro, and xenografted human tumours in vivo. In conclusion, new therapeutic strategies for which the tumour microenvironment is an asset (as opposed to a liability) are explored.