Maximal oxygen uptake (VO2max) is the main determinant of the exercise capacity and is a good predictor of life expectancy. VO2max is determined by the maximal O2 delivery (ODmax) x fractional O2 extraction (OEmax). Two main factors determine ODmax: arterial O2 content (CaO2) and maximal cardiac output (Qmax). Qmax is the product stroke volume (SV) x heart rate (HR). Since training does not increase maximal HR and barely affects CaO2, the only mechanism that could explain an increase of ODmax is a greater maximal SV. Stroke volume depends on intrinsic and extrinsic factors. Intrinsic factors are determined by the structural and functional properties of the heart, principally heart size, contractility and compliance. Extrinsic factors include: venous return, and central blood volume, mean arterial pressure (via its influence on preload). Other extrinsic factors such as sympathetic neural activity, may influence SV by regulating contractility and altering HR (and filling times). Several experiments have shown that Qmax can hardly be increased without cardiac remodelling; at most 1 l.min-1 extra Qmax can be achieved by plasma volume expansion of by reducing the afterload in some experimental settings. Since top-level endurance athletes may achieve VO2max values ~ 85 ml.kg-1.min-1 (or 6.0 l.min-1, for a body mass of 70 kg), it turns that they must be able to reach a Qmax ~ 35 l.min-1. This is achieved with an SV of 185-190 ml and a HRmax=185-190 beats.min-1. For a maximal ejection fraction of 80%, these athletes must be able to reach ~230 ml end diastolic volumes at maximal exercise, what requires a big heart. Since current studies indicate that SV can be hardly increased more tan 20-30 ml after one year of training despite remarkable heart remodelling elite athletes must have a big heart before starting training. Given that the standard deviation for VO2max is 0.6-0.7 l.min-1 in sedentary subjects, at least 2.5% of the human sedentary population could have a VO2max ≥ 4.8 l.min-1 (69 ml.kg-1.min-1) and a Qmax=28-34 l.min-1 for OEmax=0.70-0.85). These are the only humans than may have a possibility to become top-level endurance athletes. The transfer of O2 in the lung may also contribute to limit VO2max under certain circumstances; however the functional reserve of O2 lung diffusing capacity is remarkable.