Large individual differences exist in aerobic fitness in childhood and adolescence, but the relative contribution of genetic factors to this variation remains to be established. In a sample of adolescent twins and siblings (n = 479), heart rate (HR) and maximal oxygen uptake (V̇o2max) were recorded during the climax of a graded maximal exercise test. In addition, V̇o2max was predicted in two graded submaximal exercise tests on the cycle ergometer and the treadmill, using extrapolation of the HR/V̇o2 curve to the predicted HRmax. Heritability estimates for measured V̇o2max were 60% in ml/min and 55% for V̇o2max in ml·min−1·kg−1. Phenotypic correlations between measured V̇o2max and predicted V̇o2max from either submaximal treadmill or cycle ergometer tests were modest (0.57 < r < 0.70), in part because of the poor agreement between predicted and actual HRmax. The majority of this correlation was explained by genetic factors; therefore, the submaximal exercise tests still led to very comparable estimates of heritability of V̇o2max. To arrive at a robust estimate for the heritability of V̇o2max in children to young adults, a sample size weighted meta-analysis was performed on all extant twin and sibling studies in this age range. Eight studies, including the current study, were meta-analyzed and resulted in a weighted heritability estimate of 59% (ml/min) and 72% (ml·min−1·kg−1) for V̇o2max. Taken together, the twin-sibling study and meta-analyses showed that from childhood to early adulthood genetic factors determine more than half of the individual differences in V̇o2max.