The systematic increase in V˙O2 uptake and O2 extraction with increasing work rates conceals a substantial heterogeneity of O2 delivery (Q˙O2)-to- V˙O2 matching across and within muscles and other organs. We hypothesize that whether increased/decreased Q˙O2/V˙O2 heterogeneity can be judged as "good" or "bad," for example, after exercise training or in aged individuals or with disease (heart failure, diabetes) depends on the resultant effects on O2 transport and contractile performance.