The phenotypic plasticity of vertebrate species to a longer lasting reduction in atmospheric oxygen (hypoxia) has been laid out before in the context of giant insect and human altitude populations. The symposia will address the possible molecular nature of the underlying adaptive process in light of new data. These imply that distinct proteomic and mutagenic changes in components of the respiratory chain and related radical scavenging processes underlie the acquired hypoxia tolerance. Using an integrative, comparative approach it will be addressed whether this glimpse of molecular information on modified respiratory-related processes reflects a universal strategy of different taxa to tune metabolic processes under the selective pressure of hypoxia. A second aspect will be to discuss possible mechanisms that target these permanent adaptations to oxygen dependent processes and evoke phenoptypic features which remain eminent after return to normoxia in once-hypoxia adapted species.