Numerous changes are known to occur to red cells during storage which have been hypothesized to impair the function of transfused red cells in vivo. In order to understand the effect of storage on red cell function in transfusion, we need to understand events at the level of the microcirculation, the network of small arterioles, venules, and capillaries where tissue oxygenation takes place. This session, consisting of three lectures, will review the effects of storage on the red cells and provide an introduction to the microcirculation, focusing on its role in the exchange of respiratory gases and regulation of blood flow. Non-invasive tools, such as near infrared spectroscopy and orthogonal polarization spectroscopy, which are now available for clinical and research use, allow us to interrogate tissue beds and the microcirculation. With the ability to understand events at this level, we can begin to make physiology-driven decisions about RBC transfusions for patients.