Maximal oxygen uptake (VO2max) is a physiological characteristic bounded by the parametric limits of the Fick equation: (Left ventricular end-diastolic volume – LV end systolic volume) x heart rate x arterio-venous oxygen difference. "Classical" views of VO2max emphasize its critical dependence on convective oxygen transport to working skeletal muscle and recent data are dispositive, proving convincingly that such limits must and do exist. "Contemporary" investigation into the mechanisms underlying peripheral muscle fatigue due to energetic supply/demand mismatch are clarifying the local mediators of fatigue at the skeletal muscle level, though the afferent signaling pathways that communicate these environmental conditions to the brain and the sites of central integration of cardiovascular and neuromotor control are still being worked out. Elite endurance athletes have a high VO2max due primarily to a high cardiac output from a large compliant cardiac chamber (including the myocardium and pericardium) which relaxes quickly and fills to a large end-diastolic volume. This large capacity for LV filling and ejection allows preservation of blood pressure during extraordinary rates of muscle blood flow and oxygen transport which support high rates of sustained oxidative metabolism. The magnitude and mechanisms of cardiac phenotype plasticity remain uncertain and likely involve underlying genetic factors, as well as the length, duration, type, intensity and age of initiation of the training stimulus.