At high altitude, the oxygen availability is reduced due to the low barometric pressure. Humans exposed to this reduced oxygen availability experience a myriad of physiological responses aiming to defend the uptake and distribution of oxygen to the different organs. The regulatory mechanisms underlying the responses to a reduced oxygen availability are complex and remain incompletely understood despite decades of research. We aim to further advance our understanding of these mechanisms, their interplay, and their significance for altitude tolerance, physical performance, and health. Our studies range from laboratory studies in the terraXcube to field research and include both lowlanders and native highlanders as participants.