In the present issue of the European Journal of Preventive Cardiology, Montero and Dı´az-Can˜estro address a basic argument in exercise physiology, namely the cardiovascular (CV) determinants of endurance training (ET)-induced increases in VO 2max .1 Using a meta-analytic approach, the authors provide collective evidence that changes in VO 2max after an ET period in elderly healthy subjects are linearly related to those in cardiac output reached at maximal exercise (Q max ), but not to those in arterio-venous O 2 concentration differences (Ca-vO 2max ), making a solid point on what should be the CV target of ET programs. These results are in keeping with previous findings by the same group obtained in young healthy individuals.2 Since ET is one of the most impactful interventions in CV prevention, it seems relevant to put the present findings in the most appropriate perspective.Present findings are actually consistent with the body of evidence indicating O 2 delivery to skeletal muscle as the main limiting factor of peak aerobic performance during exercise, involving more than 50% of total muscle mass, such as running and cycling. This evidence has been elegantly proved in laboratory investigations comparing VO 2max , Q max and Ca-vO 2max during single-leg (knee extension) vs. two-leg (cycling) exercise in normal subjects.3,4 Such an experimental design allows the determination of the functional reserve of the peripheral links of the O 2 transport and utilization chain when freed from the O 2 delivery constraints imposed by large muscle mass use. During oneleg exercise involving around 2-3 kg of muscle, leg blood flow per unit of muscle mass is much higher (up to 2.5 L/kg/min) than that observed during twoleg exercise. The existence of a flow reserve during exercise involving a small muscle mass parallels the finding of VO 2max values as high as 250-600 mL/kg/min in human quadriceps during the same exercise model. 3,4 In addition, evidence has been put forth that muscle mitochondrial oxidative capacity at peak two-leg exercise exceeds maximal O 2 delivery in humans. 5 Overall, these findings demonstrate the existence of a large metabolic reserve, virtually excluding the possibility that the metabolic aerobic machinery of skeletal muscle is the limiting factor of peak aerobic performance. Another possible limiting factor to VO 2max is peripheral O 2 diffusing capacity, but in this regard, the available evidence is less clear. Analogously to leg blood flow and metabolic capacity, Ca-vO 2max has been found to be higher during one-leg than two-leg exercise, 6,7 but it must be acknowledged that CavO 2max is affected not only by diffusive O 2 transport, but also by O 2 delivery to the site of diffusion from skeletal muscle capillaries to mitochondria. Available data regarding diffusional O 2 conductance (which is solely a consequence of diffusive O 2 movement) in one-leg as compared to two-leg exercise in normal subjects are scarce and not conclusive. 8 On the other hand, the concept of a finite limit to cardiac outpu...