Altitude training is very popular among endurance athletes. But athletes respond very different on acute altitude exposure and altitude training. There are individual differences in the decrement of maximal oxygen consumption making general advices on the effect of altitude training very difficult. During the last few years different altitude training regimes have been developed. Beside "living high--training low," the concept of "living low--training high" becomes more and more popular. By this regime, athletes train under simulated or natural hypoxic conditions, while recovery time is spent at sea-level. Several studies show that with "living low--training high" maximal oxygen consumption as well as aerobic and anaerobic endurance performance can be improved. Molecular analysis reveal that a transcription factor called Hypoxia-Inducible Factor 1 (HIF-1) acts as a master gene in the regulation of hypoxia-dependent gene expression. In human skeletal muscle "living low-training high" induces the expression of glycolytic enzymes, the angiogenic factor VEGF, myoglobin as well as the increase of capillarity and mitochondrial content in parallel to the induction of the HIF-1 system. In trained human skeletal muscle, these adaptations cause a shift of substrate selection to an increased oxidation of carbohydrates as well as to an improvement of the conditions for transport and utilization of oxygen. Depending on the kind of sports, "living low--training high" can be used to train these muscular adaptations and to increase exercise performance.