Development of new approaches to ameliorate tumor hypoxia may require understanding of the relative importance of supply vs. demand. On the demand side, abnormalities in energy metabolism are known to be related to defects in regulation of respiratory enzymes, combined with high demand for energy caused by cell proliferation. On the supply side deficiencies in efficiency of nutrient supply, such as low vascular density and uneven vascular distribution appear to play important roles. In theoretical simulations based on actual in vivo data, however, modulation of oxygen consumption is much more efficient in affecting oxygen transport than modification of delivery.