The oxygen delivery system consists of multiple components balanced to provide optimal oxygen supply to all tissues and arranged such that an abnormality in one component is compensated by adjustments in others. Analysis of pertinent data indicates that leftward shifts of the oxygen dissociation curve (ODC) in normal animals and persons elicit adaptive changes in other components which sustain normal oxygen supply. By contrast, several recent studies indicate that leftward ODC shifts, when occurring in combination with other abnormalities of oxygen delivery, produce or aggravate hypoxia. These data suggest that the brain and heart are the organs particularly at risk. It is concluded that leftward ODC shifts, due to massive transfusion of stored blood and to hyperventilation of unconscious patients, are most likely to be hazardous in the presence of poor perfusion, coronary artery disease, or cerebrovascular disease.