An accurate assessment of regional tissue oxygen delivery (Do2) may help the intensivist to attenuate end-organ damage in critically ill patients. Transport of oxygen from the ambient air to the mitochondria occurs by convection and diffusion, and is tightly regulated by neural and humoral factors. This article reviews the basic principles of Do2 and the abnormal oxygen supply-demand relationship seen in patients with shock. It also discusses approaches to monitoring Do2, including clinical symptoms/signs, acid-base status, and gas exchange, which provide global assessment, as well as gastric tonometry, which may reflect regional Do2. Some new experimental methods, such as near-infrared spectroscopy and positron emission tomography, are still in development but may in the future provide useful clinical devices for quantifying the adequacy of regional tissue oxygenation in critically ill patients.